Myelodysplasia in VEXAS syndrome.

Introduction

VEXAS (vacuoles, E1 enzyme, X linked, autoinflammatory, somatic) syndrome was first defined in 2019 using a genotype-first approach, analyzing exome data from a cohort of patients with undiagnosed autoinflammatory diseases at the National Institutes of Health. 1 The disease-causing mutations typically occur in exon 3 of the ubiquitin-activating enzyme E1 ( UBA1 ) gene, located on the X chromosome, which encodes the master ubiquitin ligase. The most common mutations affect M41, the translational start site for the cytoplasmic isoform, UBA1b, and result in a truncated catalytically inactive isoform, UBA1c. These partial loss-of-function mutations originate in hematopoietic stem and progenitor cells (HSPC) and are restricted predominantly to the myeloid lineage in the periphery. 1 , 2 Although absent in lymphocytes, these mutations have also been found in natural killer (NK) cells, resulting in quantitative and qualitative defects and an increased risk of infections. 3 Mutated cells accumulate misfolded proteins due to reduced polyubiquitination and activation of the unfolded protein response. 4 Myeloid-driven dysregulation leads to systemic autoinflammation and progressive bone marrow (BM) failure, and has been associated with myeloid neoplasms, especially myelodysplastic syndromes (MDS). Patients with VEXAS syndrome experience a high symptom burden that significantly affects their quality of life and reduces life expectancy. 5 , 6 , 7 , 8 Population studies have identified UBA1 mutations across all ages and ancestries, with high penetrance in males over the age of 50 years and of European descent, among whom the prevalence is estimated at 1 in 4000. 9 , 10

VEXAS syndrome is often referred to as “the great mimic,” because it fulfills criteria for numerous diseases while presenting with overlapping features. Patients with UBA1 driver mutations and progressive, sustained cytopenia indicative of ineffective hematopoiesis often meet diagnostic criteria for MDS, based primarily on histomorphologic findings. However, BM findings in patients with VEXAS syndrome are often abnormal even in the absence of significant cytopenia, demonstrating hypercellularity with increased myeloid-to-erythroid ratio, cytoplasmic vacuoles in myeloid and erythroid precursors, and megakaryocytic atypia/dyspoiesis, secondary to the pervasive, often refractory, systemic inflammation and defective ubiquitination. 11 , 12 This overlap has led to MDS diagnosis in ∼30% to 50% of patients with VEXAS syndrome in some cohorts. 8 , 13 However, an increased blast percentage, high-risk cytogenetic abnormalities, and typical MDS-associated somatic mutations are infrequently reported. 12 , 14 , 15 Although some of these patients may have bona fide MDS, as supported by overt multilineage dysplasia and cytogenetic and/or genetic abnormalities characteristic of MDS (eg, SF3B1 mutations and ring sideroblasts), careful review of the literature suggests that MDS is likely overdiagnosed in patients with VEXAS syndrome, similar to the initial descriptions of myeloid malignancy predisposition syndromes (eg, RUNX1 familial platelet disorder). 12 , 16

There is currently no standard treatment for patients with VEXAS syndrome. 17 Glucocorticoid-sparing therapies include biologics targeting cytokines such as interleukin-6 (IL-6), IL-1, as well as JAK1/2 inhibitors 18 ; however, these treatments generally do not alter the progression of BM failure. 19 In patients with significant cytopenia or a diagnosis of MDS, hypomethylating agents (HMAs) are commonly used and have demonstrated both inflammatory and hematologic responses, in addition to reducing the mutant UBA1 clonal burden. 20 , 21 For selected fit patients with appropriate donor sources, hematopoietic stem cell (HSC) transplantation remains a potentially curative option, with good outcomes being reported in limited series of patients. 22 , 23

This review aims to explore the distinct features of MDS in VEXAS, highlighting the challenges of diagnosing MDS in the context of VEXAS syndrome and underscoring the unique clinical and molecular features and prognostic outcomes.

UBA1 mutational landscape and clonal dynamics

VEXAS syndrome is defined by the presence of UBA1 mutations in a patient with signs and symptoms of inflammation and/or peripheral cytopenia. 18 Canonical mutations, specifically M41 missense and splice variants, lead to significantly decreased translation of the cytoplasmic UBA1 isoform, UBA1b. Instead, a shorter, catalytically inactive isoform, UBA1c, is produced. Residual UBA1b activity is lowest in M41V compared with M41T and M41L hot spot variants, correlating with inferior survival outcomes in patients with M41V variants. 5 Additional variants in exon 3, p.Tyr55 and p.Ser56, as well as p.Gly477, p.Ala478, p.Asp506, p.Asp585, p.Ser621, and p.Ile894 in the adenylation domain, have been reported and exhibit a VEXAS syndrome phenotype. 15 , 24 , 25 , 26 Unlike the canonical UBA1 mutations, these “noncanonical” UBA1 mutations result in decreased catalytic activity of both nuclear and cytoplasmic isoforms through distinct mechanisms, including impairing adenylation or thiolation, ultimately leading to a bottleneck in ubiquitin transfer to E2 enzymes. 26 Interestingly, although most cases with noncanonical UBA1 variants have inflammatory manifestations, the hematologic findings are distinct from those with canonical M41 mutations ( Table 1 ). In patients with noncanonical mutations in the adenylation domain, hemolysis markers are elevated, along with notable erythroid hyperplasia in the BM. 25 Table 1. Functional impact of UBA1 mutations and reported BM aberrations and hematologic diagnosis Gene domain Variants Functional impact Marrow findings Heme malignancies Canonical mutations IAD exon 3 and splice site variants M41V, M41T, M41L Altered UBA1b expression, catalytically inactive form present (UBA1c) Myeloid hyperplasia, erythroid hypoplasia, megakaryocytic atypia, cytoplasmic vacuoles MDS, AML, CMML, aCML c.118-1G>C, c.118-2A>C, c.119G>C Noncanonical mutations IAD exon 3 S56F Reduce catalytic activity of UBA1a and UBA1b by rendering thiolation thermolabile Left shifted myeloid, erythroid hyperplasia, megakaryocytic atypia, ± cytoplasmic vacuoles MDS Y55H AAD exon 14 G477A Reduce catalytic activity of UBA1a and UBA1b by reduction in thiolation Marked erythroid hyperplasia and dysplasia in all lineages, cases with absent cytoplasmic vacuoles MDS D506N D506G Reduce catalytic activity of UBA1a and UBA1a by reduction in thiolation Details NA MDS A478S Reduce catalytic activity of UBA1a and UBA1b by aberrant oxyester formation Details NA MDS, AML, cutaneous ALCL S621C Reduce catalytic activity of UBA1a and UBA1b by aberrant oxyester formation Marked erythroid hyperplasia, cytoplasmic vacuoles may not be present MDS D585A D585E NA Details NA, cytoplasmic vacuoles present NA Unknown AAD exon 14 N606I NA NA MDS Splice site variant c.346-2A>G NA Details NA, cytoplasmic vacuoles present CLL and MDS AAD exon 24 I894S I894F NA Details NA, cytoplasmic vacuoles present MDS AAD, active adenylation domain; aCML, atypical CML; ALCL, anaplastic large-cell lymphoma; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; IAD, inactive adenylation domain; M, methionine; NA, not available; T, threonine; UBA1a, nuclear UBA1 isoform; UBA1b/UBA1c, cytoplasmic isoforms; V, valine.

Several other UBA1 variants have since been documented, with many of these variants being subclonal, needing further mechanistic elucidation. 24 Additionally, the presence of multiple mutations in a single individual but in distinct clones has also been reported, indicative of a selective pressure advantage. 14 , 25 , 27

Altered hematopoiesis in VEXAS syndrome

HSPCs in VEXAS syndrome exhibit somatic mosaicism, comprising both UBA1 -mutated and wild-type cells. UBA1 -mutated HSPCs are reprogrammed toward myeloid differentiation, exhibit enhanced inflammation, and have upregulated ubiquitin proteasome response pathways. Single-cell multiomics studies have elucidated the cellular pathways affected by somatic mutations in UBA1 , leading to the altered hematopoiesis observed in VEXAS syndrome ( Figure 1 ). 4 , 28 , 29 Figure 1. Ineffective and biased hematopoiesis with mosaic UBA1 mut and UBA1 –wild-type HSCs in VEXAS syndrome. This figure has 3 sections. The first shows the cell type specific tolerance of UBA1 mutations and compartment expansion or reduction as a result. Hematopoiesis is myeloid predominant with reduced erythropoiesis. The lymphoid compartment is quantitatively altered and qualitatively defective with T and B lymphocytes mostly deriving from UBA1 wild-type stem and progenitors whereas NK cells from UBA1 mut and wild-type cells. The BM microenvironment is high inflammatory with increase in tumor necrosis factor α and interferon gamma cytokines, represented by the small circles in blue, yellow, and red. As a result, BM examination (second section) typically shows hypercellularity with an increased M:E ratio, cytoplasmic vacuoles in myeloid and erythroid precursor cells, and megakaryocytic atypia including so-called pink-belly or signet-ring megakaryocytes with peripheralized nuclei and prominent eosinophilic cytoplasm. In the peripheral blood (third section), complete blood counts with a differential in patients with VEXAS syndrome often demonstrate macrocytosis > macrocytic anemia > lymphopenia > monocytopenia > thrombocytopenia. Neutrophils may be increased, normal or rarely reduced, and depend on the state of inflammation. Neutrophils may demonstrate hyposegmentation or pelgeroid morphology. Figure created with biorender.com . Patel B. (2026) https://biorender.com/68e3dc5cbeb698e8bb1a27ef . M:E, myeloid-to-erythroid; UBA1 mut , UBA 1 -mutated.

Clinically, peripheral blood examination commonly reveals anemia, lymphopenia, monocytopenia, and thrombocytopenia, with normal to elevated absolute neutrophil counts. Hematopoiesis in VEXAS syndrome is intrinsically skewed toward myelopoiesis, and this process appears to be progressive in longitudinal studies. 11 , 19 , 28 Tolerance to UBA1 mutations is specific to cell state and cell type. Single-cell RNA sequencing of wild-type and UBA1 -mutated BM mononuclear cells and enriched HSPCs from patients with VEXAS syndrome revealed increased cell cycling of myeloid cells, particularly mutated cells, whereas lymphoid-committed progenitors demonstrated increased apoptosis. 4 , 28 Additionally, the HSPC compartment in the BM of patients with VEXAS syndrome show reduced HSPC and multipotent progenitor cells with expanded common myeloid progenitors and early T-cell progenitors. 30 In the periphery, circulating CD34 + HSPCs, especially myeloid progenitors, are higher in patients with VEXAS syndrome than in healthy controls.

Master transcription factors involved in hematopoietic lineage specification are altered in VEXAS syndrome. Expression of PAX5 (to lymphoid progenitors) and GATA1 (to megakaryocyte-erythroid progenitors differentiation) are decreased, whereas SPI1 (encoding PU.1, to granulocyte-monocyte progenitors [GMP] differentiation) levels are increased. Additionally, CEBPA (from GMP to granulocytes) expression is higher, whereas IRF8 (GMP to monocyte) expression is decreased in VEXAS syndrome samples compared with matched healthy controls. 28 These findings indicate early lineage priming in UBA1 -mutant HSPCs toward myeloid differentiation and against erythroid and lymphoid differentiation, with the myeloid differentiation demonstrating a neutrophil maturation bias. 4 , 28

Impaired ubiquitination in UBA1 -mutant HSPCs would be expected to result in proteomic stress and cell death; however, a recent study suggests that prosurvival signals through IRE1, PERK, and ATF4 in endoplasmic reticulin stress response, along with a global reduction in protein translation allow these cells to avoid apoptosis. 4 PERK activation is also linked to myeloid-biased differentiation, which is abrogated with inhibition of PERK. Laboratory studies using primary patients cells has been challenging. Patient-derived CD34 + cells exhibit poor engraftment in immunodeficient mice and have reduced in vitro differentiation potential, indicating the vital role of the BM microenvironment and cell-cell interactions. 30

Experimental models in cell lines using CRISPR-CRISPR–associated protein 9 knockin and base editing have further unraveled mechanisms driving UBA1 -mutant clonal dominance in VEXAS syndrome. 30 , 31 Both models recapitulated cellular hallmarks of VEXAS syndrome and demonstrated exclusive myeloid colony-forming potential. A humanized xenograft model of VEXAS syndrome generated by transplanting base-edited UBA1 -mutant HSPCs phenocopied early priming of VEXAS HSCs and multipotent progenitor cells toward myeloid differentiation, lymphoid lineage arrest, and ineffective erythropoiesis, as observed in patients. Proerythroblasts negatively tolerate UBA1 mutations, and impaired erythropoiesis is conducted by wild-type cells. 32 Early erythroid lethality is a result of defective ubiquitylation, overexpression of TP53, and alteration of ribosome biogenesis in mutant- UBA1 cells in vitro. 32 Hence, the degree of anemia in patients with VEXAS syndrome may be determined by wild-type erythroblasts.

Competitive transplantations of UBA1 -mutant and UBA1 –wild-type HSPCs reveal paracrine poisoning of wild-type HSPCs from the cell-extrinsic inflammatory microenvironment created by UBA1 -mutant progeny. Meanwhile, UBA1 -mutant cells shield themselves from inflammation-induced apoptosis and immune clearance by entering dormancy or undergoing senescence. 30 Over time, the selective survival of the mutant population and regression of wild-type HSCs likely lead to progressive BM failure, explaining the progressive cytopenia(s) clinically observed in VEXAS syndrome.

Predominantly UBA1 -mutated HSPCs and myeloid cells from patients with VEXAS syndrome display activated inflammatory signatures, particularly interferon gamma and tumor necrosis factor α, indicating cell-autonomous mechanisms of inflammation. In the inflammatory milieu, there is increased cross talk between UBA1 -mutated HSPCs and myeloid cells creating a vicious cycle of relentless inflammation in this disease. Similar inflammatory enhancement is also found in other myeloid neoplasms with autoimmune overlap including MDS, chronic myelomonocytic leukemia, chronic myeloid leukemia, but to a significantly lesser degree. 28 In a cohort of patients with systemic inflammation who tested negative for pathogenic UBA1 variants, IDH1/2 mutations were significantly enriched, indicating presence of other somatic genomic drivers of autoinflammation in patients with UBA1 -negative disease that present with clinical manifestations similar to VEXAS syndrome. 33 Additionally, enhanced inflammatory signatures, upregulation of apoptotic genes, and negative enrichment of cell cycle–related genes were also observed in T and B lymphocytes, indicating a paracrine effect of proinflammatory mutant cells on their wild-type counterparts. 30 Furthermore, broad immune dysregulation including inflammation and alterations in myeloid, NK, and T cells 3 , 29 , 34 may contribute to the progression to MDS/marrow failure. In addition, quantitative and qualitative defects in monocytes and NK cells predispose patients to intracellular and opportunistic infections 29 , 34 , 35 , 36

Peripheral blood features in VEXAS syndrome

Peripheral blood counts are often abnormal in patients with VEXAS syndrome. Most common abnormalities include macrocytosis/macrocytic anemia (90%) followed by monocytopenia (50%-70%). 11 , 12 Moderate to severe thrombocytopenia and neutropenia are less frequent, seen in ∼30% and 20% of patients, respectively. Lymphopenia is also common (60%-80%), with a prominent decrease in B cells compared with T cells. 14 Cytopenia generally occur along with rheumatologic and inflammatory symptoms but progressively worsen. Indeed, in 1 study, the presence of anemia and thrombocytopenia in the right clinical setting had a high predictive value for a diagnosis of VEXAS syndrome. 5 Transfusion-dependent anemia is reported in ∼1 of 3 patients with VEXAS syndrome. 14

Peripheral blood smear review typically shows macrocytes and rouleaux formation in a small subset of patients. 12 Circulating nucleated red blood cells are relatively uncommon (10%). In half of the cases, neutrophils have toxic granulation, and a granulocytic left shift to the myelocyte stage of maturation is observed in 30% to 40% of patients. Circulating blasts are rare. Neutrophils may display features of dysgranulopoiesis, primarily as hyposegmentation/Pelger-Huët–like morphology. Cytoplasmic vacuolization in circulating immature and mature myeloid cells can be seen; however, this is not a finding specific for VEXAS syndrome and is observed in patients with UBA1 -negative MDS. 37 , 38 , 39 , 40 Compared with other systemic inflammatory diseases, peripheral cytologic analysis of patients with VEXAS syndrome reveals increased immature neutrophils and greater number of vacuoles. 41 Platelet morphology is predominantly normal (normal size and well granulated). Lymphocytes show a range of cytologic features, bland to granulated and reactive ( Figure 1 ).

BM features in VEXAS syndrome

The most common BM presentation in VEXAS syndrome is that of a hypercellular BM with granulocytic hyperplasia often left-shifted, vacuoles in myeloid and erythroid precursors, no increase in blasts, and with or without dyspoiesis. 12 , 42 BM cytoplasmic vacuoles in myeloid and erythroid precursors is a key feature of VEXAS syndrome and is typically evident on review of BM aspirate smears. 1 , 42 Cytoplasmic vacuoles are common in erythroid and myeloid precursors but may also be found in megakaryocytes. 38 , 39 This finding is not specific for VEXAS syndrome and is not a marker of myelodysplasia, as it can be seen in other conditions, including nonmalignant diseases such as copper deficiency, zinc toxicity, and ethanol abuse. 43 , 44

Megakaryocytes often show abnormal or atypical morphology including forms with peripheralized nuclei and prominent eosinophilic condensed cytoplasm representing so-called signet-ring or pink-belly megakaryocytes 12 , 45 ( Figure 1 ). When dyspoiesis is present in the myeloid lineage, one commonly sees hyposegmented or pseudo–Pelger-Heüt neutrophils, but these are typically <10% of the myeloid lineage ( Figure 2 ). Erythroid dyspoiesis commonly involves binucleation or multinucleation involving <10% of erythroid precursors. Some cases may demonstrate a profound erythroid hypoplasia. 11 Plasma cells may be increased, mostly polytypic with normal immunophenotype. However, in a small proportion of patients, clonal plasma cells with aberrant loss of CD19, or expression of CD56, are detected (monoclonal gammopathy). Figure 2. VEXAS syndrome with BM dyspoiesis from patients without significant cytopenia. (A) BM aspirate showing dyspoietic, hyposegmented, and pelgeroid neutrophils present in <10% of myeloid cells. (B) Vacuolated precursors and mild dysmyelopoiesis with binucleated myelocyte. (C) Dyspoietic and multinucleated erythroid precursors.

Genetic and clinical features of MDS in VEXAS syndrome

MDS are myeloid neoplasms characterized by clonal proliferation of HSPCs, recurrent somatic genetic abnormalities (somatic mutations and copy number alterations), ineffective hematopoiesis with dysplasia culminating in peripheral blood cytopenia, and an inherent risk for evolution to acute myeloid leukemia (AML). 46 Important diagnostic criteria include persistent and unexplained cytopenia in ≥1 peripheral blood lineages, morphologic dysplasia in ≥1 BM cell lineages (comprising >10% of cells in the involved lineage[s]), an increase in peripheral blood/BM blasts, and presence of somatic mutations and/or cytogenetic abnormalities. 46 , 47 Although somatic mutations can be seen in almost all patients with MDS, cytogenetic abnormalities are seen in only half of cases. With the exception of MDS with del(5q), the 2022 World Health Organization (WHO) classification system eliminated MDS-defining cytogenetic abnormalities, whereas the International Consensus Classification (ICC) system retained del(7q)/-7 and complex karyotypes. 46 , 47 The most frequent somatic mutations seen in ∼10% or more of patients with MDS, in descending order of frequency, include TET2 , ASXL1 , SF3B1 , DNMT3A , SRSF2 , RUNX1 , and TP53 . 48 Although morphologic dysplasia is an important hallmark for MDS diagnosis, several of these features are not specific to MDS and can be seen in nonclonal disorders such as nutritional deficiencies, toxin exposures, and congenital syndromes, and as a component of inflammatory disorders 49 This is well highlighted by the fact that baseline atypia, especially involving megakaryocytes can be seen in germ line disorders such as RUNX1 -FPD, and the fact that ring sideroblasts can be seen in congenital sideroblastic anemias ( ALAS2 mutations), without risk for malignant transformation. 50 , 51 MDS transformation to AML is dependent on distinct genetic pathways and clonal selection. 48 , 52 , 53

In VEXAS syndrome, apart from the disease-defining UBA1 mutation, somatic mutations can be seen in ∼60% of patients, with the clonal hematopoiesis landscape being dominated by DNMT3A and TET2 mutations, even in patients with an MDS diagnosis. 14 , 54 Somatic mutations classically seen in MDS involving RNA splicing and signaling genes, and the DNA damage response and repair pathway, along with ICC recommended MDS-defining cytogenetic abnormalities, are infrequent. In our previous study, using single-cell DNA sequencing in a patient with VEXAS syndrome and a SF3B1 mutation, we showed that the SF3B1 mutation was present in a smaller, independent clone, whereas the UBA1 -mutated clone demonstrated clear clonal dominance. 14 Conversely, DNMT3A mutations are often seen with high variant allele fractions (median, ∼30%) and tend to be in the same clone as mutant UBA1 , often preceding it. Similarly, TET2 mutations are also typically found in the same clone as mutant UBA1 but mostly follow mutant UBA1 in clonal positioning, with lower median variant allele fractions than DNMT3A mutations. In summary, in VEXAS syndrome, the clonal hierarchy is dependent on timing of mutational acquisition, clonal positioning, and clonal location in relation to UBA1 mutant clones. DNMT3A/TET2 mutations have been associated with adverse survival outcomes, without an increased risk of AML transformation, although most DNMT3A mutations occur in the methyltransferase domain, with ∼10% having the AML-associated DNMT3A R882 hot spot mutation. Hence, although a subset of cases show overt MDS-defining BM dysplasia, in the setting of pervasive systemic inflammation, impaired ubiquitination, and a relatively unique somatic mosaic landscape, it is unclear whether all patients with these findings have bona fide MDS ( Figure 3 ). In a recent study, use of the Revised and Molecular International Prognostic Scoring System for prognostic discrimination was limited in patients with VEXAS syndrome with MDS, and survival was shorter in these patients than in MDS controls. 54 Figure 3. Common features of MDS in VEXAS syndrome. This figure summarizes the epidemiology, clinical manifestations, laboratory finding abnormalities, histomorphology on BM examination, risk of AML), and management in patients with VEXAS syndrome who are diagnosed with MDS. IPSS-R, Revised International Prognostic Scoring System. Figure created with biorender.com . Patel B. (2026) https://biorender.com/6984b82fb3f2c1ab6f1b6627 .

Another feature of MDS in VEXAS syndrome is the very low risk of AML transformation, with only few cases having been reported thus far. 15 , 24 , 55 In 1 report, all AML cases identified had UBA1 -mutant subclones, as indicated by very low mutational burdens, along with clonal dominant aberrations involving myeloid drivers such as FLT3 , RAS , and del7q. 15 The clinical relevance of these subclones in bona fide myeloid neoplasms and their ability to develop VEXAS syndrome–like features, remains to be defined. A lower risk of MDS progression to AML in patients with VEXAS syndrome may be explained by the underlying genetic ontogeny, in addition to inherent hematopoietic fitness constraints associated with canonical UBA1 mutations that are potentially not conducive for classical genomic alterations implicated in MDS-to-AML transformation.

Diagnosis of MDS in VEXAS syndrome

A subset of VEXAS syndrome BM cases shows frank morphologic dysplasia based on WHO/ICC criteria, which is often multilineage ( Figure 4 A). 11 , 42 In addition to the atypical megakaryocytic forms described earlier, mononuclear megakaryocytes, micromegakaryocytes, and forms with separated nuclear lobes may be seen representing >10% of megakaryocytes. Dysmyelopoiesis may include hypogranular or hyposegmented forms, or marked nuclear-cytoplasmic asynchronous maturation, in >10% of the myeloid cells. Dyserythropoiesis is evidenced by binucleation, multinucleation, nuclear budding, and/or megaloblastic changes involving >10% of the erythroid lineage. Ring sideroblasts may be present on iron stain with detection of SF3B1 mutation in few cases. 1 Rare cases may demonstrate increased blasts consistent with MDS with excess blasts 14 , 15 ( Figure 4 B). Plasma cells may be increased and may be clonal, representing monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or myeloma. 42 Flow cytometry analysis is critical for identifying abnormal immunophenotypic lineage maturation, aberrant expression of surface markers consistent with dysplasia, increased and/or abnormal blast populations, or clonal plasma cells. In all cases, the morphologic findings must be correlated with the degree of cytopenia, cytogenetics, fluorescence in situ hybridization, somatic mutation analysis, and other relevant laboratory testing. Given that there are cases of pancytopenia that improve with high-dose steroids 56 and that a high degree of active inflammation may show heightened atypia, BM examination should be avoided during an episode of acute inflammation. Progressive cytopenia despite good inflammatory control, especially in patients requiring blood transfusions is predictive of overt BM dysplasia. 14 , 57 Figure 4. MDS in VEXAS syndrome. (A) MDS with ring sideroblasts and SF3B1 mutation. From left to right, panels show hypercellular marrow with dysplastic megakaryocytes, dysplastic multinucleated precursor and asynchronous myeloid maturation (hypogranular and hyposegmented cells), dysmyelopoiesis with binucleated myelocyte, and ring sideroblasts on iron stain. Cytogenetics showed 45,X,-Y[8], XY[12] and next-generation sequencing (NGS) showed SF3B1 (variant allele fraction [VAF] of 15%), UBA1 M41V (VAF of 43%), and TET2 (VAF of 3%) at the time of the marrow analysis. (B) MDS with excess blasts. From left to right, panels show hypercellular marrow with myeloid hyperplasia with left shift, CD34 immunohistochemistry highlights increased positive cells (8%) consistent with myeloblasts, confirmed by flow cytometry, and BM aspirate showing vacuolated precursors and multiple blasts with dispersed fine chromatin and high nuclear-to-cytoplasmic ratio. Cytogenetics revealed 45,X,-Y[18],XY[2] and NGS showed UBA1 M41V (65%).

The diagnosis of MDS in patients with VEXAS syndrome with cytogenetic and/or genetic abnormalities associated with MDS, or in the presence of increased blasts is relatively straightforward. However, many patients with VEXAS syndrome receive an MDS diagnosis based on histomorphology alone. Given the high degree of baseline dyspoiesis in VEXAS syndrome that may overlap with morphologic dysplasia, caution is warranted in rendering a diagnosis of MDS without characteristic genomic aberrations or increased blasts, and close attention to the clinical setting is imperative. This includes (1) status of systemic inflammation at the time of BM examination, and (2) degree of peripheral cytopenia and comprehensive workup to exclude other causes, including medication toxicity, anemia of chronic inflammation, or active infection. Sustained and progressive cytopenia, especially requiring transfusions, with overt dysplasia, often multilineage, is highly suggestive of a diagnosis of MDS in VEXAS syndrome. A similar approach to the diagnosis of MDS has been recommended for patients with inherited BM failure syndromes and germ line predisposition to myeloid malignancy in which baseline dyspoiesis in the marrow may be prominent and should not be overinterpreted as MDS without other supporting evidence. 58 MDS that occurs in the setting of VEXAS syndrome has distinct clinical, morphologic, and molecular features. Proper diagnosis may inform therapeutic decisions and aid in clinical trial design for therapeutics development.

Therapy for patients with VEXAS syndrome with marrow failure or MDS

For this focused review, therapeutic discussion is focused on HMAs. Except for HSC transplantation, HMAs are the only therapy that have demonstrated molecular responses and long-term remissions. 20 , 59 Decrease in clonal burden correlates with an improvement in blood counts and reduction in systemic inflammation best evidenced by glucocorticoid sparing. In the absence of standardized clinical response criteria, it is difficult to know the exact rates of responses; however, in 2 major trials reported in the French cohorts (retrospective assessment for UBA1 mutation status), hematologic responses were approximated at 60% to 70%, whereas overall inflammatory responses were in the 50% to 60% range. 20 , 60 Interestingly, in a phase 2 study that identified patients with UBA1 mutation retrospectively, the responses were similar in patients with and without UBA1 mutations, indicating the immunomodulatory effects of azacitidine beyond molecular control of disease in VEXAS syndrome. 60

The timing of hematologic improvement is reported to be rapid, whereas inflammatory control may lag even in those with molecular response. Sustained remissions are described while on therapy but few groups have reported ongoing clinical remission off azacitidine after 6 cycles of standard treatment. 61 , 62 In the large FRENVEX study, among 50 patients who had achieved inflammatory response, 7 patients experienced disease relapse while on treatment, at median of 13 months, and 9 of 12 patients who discontinued azacitidine experienced disease relapse after a median of 3 years. 20 Relapses after months to years of treatment discontinuation indicates that the clonal expansion of UBA1 -mutated cells may not be rapid. 20 In the presence of an expanded UBA1 -mutant clone, there may be a feed-forward loop that sustains the clone. In relapsed cases, reinitiation of treatment with HMAs can achieve clinical responses in a subset of patients. Molecular responses with reductions in the UBA1 -mutant clone sizes have been reported by several groups but true clonal dynamics and trajectories are not clear given varying time of assessment and methodologies and samples used for sequencing. In the FRENVEX study, after a median of 10 cycles of azacitidine, 17 of 40 (42%) patients had UBA1 mutation variant allele frequencies of <2%. 20 Reduction or eradication of UBA1 -mutant clones raises a theoretical concern for progression of clonal disease in patients who have comutations in MDS-related genes.

Toxicities, particularly infection and early deaths within the first 6 cycles are notable with azacitidine treatment in VEXAS syndrome. 20 , 21 , 60 Therefore, although effective, azacitidine therapy is likely applicable to select fit patients who have a predominantly inflammatory phenotype and are refractory to targeted biologic treatments such as IL-6 or JAK inhibitors, 63 or have a predominant hematologic phenotype and a diagnosis of MDS. 20 Underlying etiology of anemia may be multifactorial in some patients and anemia of chronic uncontrolled inflammation needs to be considered. Indeed, 15% to 30% of patients have been reported to achieve transfusion independence with JAK inhibitors and IL-6 treatment. 63 Improvement in anemia has also been noted with increased doses of glucocorticoids and other immunosuppressive treatments, underscoring the role of inflammation and hepcidin-mediated anemia of inflammation as a cause in a subset of patients with VEXAS syndrome. 64

There are alternative therapies for isolated anemia that are effective in 40% of cases and have a safer toxicity profile that could be considered for older, frail patients, including erythropoiesis stimulating agents and luspatercept. 65

Hematologic malignancies beyond MDS

Although MDS is the most commonly associated hematologic malignancy in VEXAS syndrome with canonical UBA1 mutations, plasma cell dyscrasias have been described in many small case series. 11 , 66 , 67 However, the incidence and characterization of plasma cell dyscrasia is incomplete. Putative noncanonical UBA1 variants, in contrast, have been identified in various hematologic malignancies but their role in disease pathogenesis is unclear, because in many instances these mutations are subclonal. 24 Clonal competitions between UBA1 -mutated HSPCs and established driver mutations in myeloproliferative neoplasms such as BCR :: ABL1 , CALR , and JAK2V617F have also been described, with disease manifestation of myeloproliferative neoplasms, VEXAS syndrome, or both, depending on the dominant clone. 68 , 69 , 70

Conclusions and future direction

Proteostasis is cell-type dependent and impairment in ubiquitinylation because of somatic UBA1 mutations disrupts this vital cellular process. UBA1 -mutated HSCs show upregulation of prosurvival and inflammation pathways resulting in their expansion at the expense of wild-type HSCs. Myeloid-predominant hematopoiesis creates an unrelenting inflammatory state within the marrow, peripheral blood, and various tissues. Erythroid hypoplasia, megakaryocytic hyperplasia and atypia, as well as deregulated lymphoid compartments account for commonly reported blood count abnormalities, notably, macrocytic anemia, monocytopenia, and lymphopenia. Patients with VEXAS syndrome have a predisposition to myeloid neoplasms, particularly MDS, but there are diagnostic challenges given baseline abnormalities in peripheral blood counts, BM morphology, and absence of typical MDS-associated genomic alterations. This review underscores context-dependent assessment of BM findings to establish a diagnosis of MDS. Therapeutic success using traditional MDS therapies provides an added layer of complexity but the mechanisms of action of HMAs in VEXAS syndrome is not fully understood and this should not influence MDS diagnosis.

For a disease described merely 6 years ago, there have been tremendous scientific advances to expand our knowledge of biology as well as clinical phenotypes owing to collaborative international efforts. However, prospective data are still maturing and having longitudinal data in the coming years will provide insights into disease course as it relates to marrow failure and progression to MDS, especially with better control of systemic inflammation as well as earlier VEXAS syndrome diagnosis and treatment. Dynamics of the disease course will also inform future therapeutic development.

Conflict-of-interest disclosure: M.M.P. reports research funding from Kura Oncology, Stemline, Epigenetix, Polaris, and Solu Therapeutics; and has served on the advisory boards for GSK, AstraZeneca, and Sobi. The remaining authors declare no competing financial interests.

References

1 Beck DB Ferrada MA Sikora KA Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease N Engl J Med 383 27 2020 2628 2638 33108101 10.1056/NEJMoa2026834 PMC7847551

2 Sakuma M Haferlach T Walter W UBA1 dysfunction in VEXAS and cancer Oncotarget 15 1 2024 644 658 39347709 10.18632/oncotarget.28646 PMC11441413

3 Breillat P Carbone F Lereclus E Impaired cytotoxic function and exhausted phenotype of natural killer cells in VEXAS syndrome Blood 146 16 2025 1950 1963 40729686 10.1182/blood.2024028216

4 Ganesan S Murray RM Sotelo J Single-cell genotype-phenotype mapping identifies therapeutic vulnerabilities in VEXAS syndrome bioRxiv Preprint posted online 20 May 2024 10.1101/2024.05.19.594376

5 Ferrada MA Savic S Ospina Cardona D Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis Blood 140 13 2022 1496 1506 35793467 10.1182/blood.2022016985 PMC9523373

6 Efficace F Krepper D Sparano F Fazi P Voso MT Gurnari C Exploring patient-reported outcomes and morbidity burden of patients with VEXAS syndrome: a scoping review EClinicalMedicine 86 2025 103354 10.1016/j.eclinm.2025.103354 PMC12280344 40697958

7 Patel BA Groarke EM Shalhoub R Patient reported outcomes in VEXAS syndrome Blood 144 suppl 1 2024 3711

8 Georgin-Lavialle S Terrier B Guedon AF French VEXAS Group GFEV, GFM, CEREMAIA, MINHEMON Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients Br J Dermatol 186 3 2022 564 574 34632574 10.1111/bjd.20805

9 Beck DB Bodian DL Shah V Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population Jama 329 4 2023 318 324 36692560 10.1001/jama.2022.24836 PMC10408261

10 Corty RW Brogan J Byram K Springer J Grayson PC Bick AG VEXAS-defining UBA1 somatic variants in 245,368 diverse individuals in the NIH all of US cohort Arthritis Rheumatol 76 6 2024 942 948 38225170 10.1002/art.42802 PMC11410361

11 Obiorah IE Patel BA Groarke EM Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1 Blood Adv 5 16 2021 3203 3215 34427584 10.1182/bloodadvances.2021004976 PMC8405186

12 Olteanu H Patnaik M Koster MJ Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: a single-institution longitudinal study of 111 bone marrow samples from 52 patients Am J Clin Pathol 161 6 2024 609 624 38413044 10.1093/ajcp/aqad186

13 Koster MJ Kourelis T Reichard KK Clinical heterogeneity of the VEXAS syndrome: a case series Mayo Clin Proc 96 10 2021 2653 2659 34489099 10.1016/j.mayocp.2021.06.006

14 Gutierrez-Rodrigues F Kusne Y Fernandez J Spectrum of clonal hematopoiesis in VEXAS syndrome Blood 142 3 2023 244 259 37084382 10.1182/blood.2022018774 PMC10375269

15 Sirenko M Bernard E Creignou M Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes Blood 144 11 2024 1221 1229 38687605 10.1182/blood.2023023723 PMC12060156

16 Narla A When to worry about inherited bone marrow failure and myeloid malignancy predisposition syndromes in the setting of a hypocellular marrow Hematology 2021 1 2021 153 156 34889379 10.1182/hematology.2021000246 PMC8791095

17 Heiblig M Patel BA Groarke EM Bourbon E Sujobert P Toward a pathophysiology inspired treatment of VEXAS syndrome Semin Hematol 58 4 2021 239 246 34802546 10.1053/j.seminhematol.2021.09.001

18 Mekinian AM Georgin-Lavaille S Ferrada MA American College of Rheumatology guidance statement for diagnosis and management of VEXAS developed by the International VEXAS Working Group expert panel Arthritis Rheumatol 78 3 2025 509 522 40787890 10.1002/art.43287 PMC12991921

19 Turturice BA Fike A Patel BA Disease trajectories and glucocorticoid exposure in VEXAS syndrome treated with cytokine-directed therapies Ann Rheum Dis 85 2 2025 370 378 40581580 10.1016/j.ard.2025.05.021 PMC12276827

20 Jachiet V Kosmider O Beydon M Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from FRENVEX Blood 146 12 2025 1450 1461 40373272 10.1182/blood.2024028133

21 Trikha R Kong KL Galloway J De-escalation of corticosteroids and clonal remission in UBA1 mutation-driven VEXAS syndrome with 5-azacytidine Haematologica 109 10 2024 3431 3434 38867587 10.3324/haematol.2024.285519 PMC11446246

22 Gurnari C Koster L Baaij L Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT Blood Adv 8 6 2024 1444 1448 38330178 10.1182/bloodadvances.2023012478 PMC10955646

23 Mangaonkar A Langer KJ Lasho T Pilot prospective study of reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in patients with Vexas syndrome Transpl Cell Ther 30 2 2024 S292

24 Sakuma M Blombery P Meggendorfer M Novel causative variants of VEXAS in UBA1 detected through whole genome transcriptome sequencing in a large cohort of hematological malignancies Leukemia 37 5 2023 1080 1091 36823397 10.1038/s41375-023-01857-5 PMC10169658

25 Faurel A Heiblig M Kosmider O Recurrent mutations of the active adenylation domain of UBA1 in atypical form of VEXAS syndrome Hemasphere 7 4 2023 e868 10.1097/HS9.0000000000000868 PMC10043588 36999004

26 Collins JC Magaziner SJ English M Shared and distinct mechanisms of UBA1 inactivation across different diseases EMBO J 43 10 2024 1919 1946 38360993 10.1038/s44318-024-00046-z PMC11099125

27 Podvin B Cleenewerck N Nibourel O Three UBA1 clones for a unique VEXAS syndrome Rheumatology 63 2 2024 e48 e50 37698981 10.1093/rheumatology/kead472

28 Wu Z Gao S Gao Q Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS Cell Rep Med 4 8 2023 101160 10.1016/j.xcrm.2023.101160 PMC10439277 37586319

29 Kosmider O Possémé C Templé M VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation Nat Commun 15 1 2024 910 38291039 10.1038/s41467-024-44811-4 PMC10828464

30 Molteni R Fiumara M Campochiaro C Mechanisms of hematopoietic clonal dominance in VEXAS syndrome Nat Med 31 6 2025 1911 1924 40195449 10.1038/s41591-025-03623-9 PMC12176642

31 Chiaramida A Obwar SG Nordstrom AEH Sensitivity to targeted UBA1 inhibition in a myeloid cell line model of VEXAS syndrome Blood Adv 7 24 2023 7445 7456 38091008 10.1182/bloodadvances.2023010531 PMC10758730

32 Rodrigues F Hardouin G El Hoss S VEXAS syndrome anemia is a mosaic erythroblastopenia Blood 147 11 2026 1178 1190 40971475 10.1182/blood.2025029081

33 Castellan FMG Wong M Johansson K IDH1/2 somatic hotspot mutations as independent drivers of autoinflammation [abstract] Arthritis Rheumatol 77 suppl 9 2025

34 Mizumaki H Gao S Wu Z In depth transcriptomic profiling defines a landscape of dysfunctional immune responses in patients with VEXAS syndrome Nat Commun 16 1 2025 4690 40394087 10.1038/s41467-025-59890-0 PMC12092610

35 Czech M Cuellar-Rodriguez J Patel BA Opportunistic infections, mortality risk, and prevention strategies in patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome Open Forum Infect Dis 11 7 2024 ofae405 10.1093/ofid/ofae405 PMC11285395 39077052

36 Ribier V Hadjadj J Jachiet V Mapping the infectious burden in VEXAS syndrome: a systematic review and rationale for prevention Lancet Rheumatol 7 10 2025 e734 e744 40915301 10.1016/S2665-9913(25)00225-5

37 Tosato F Pelloso M Zuin J Basso D Peripheral blood cells vacuoles in VEXAS syndrome Am J Hematol 98 10 2023 1663 1664 37073682 10.1002/ajh.26931

38 Lacombe V Hadjadj J Georgin-Lavialle S Lavigne C Geneviève F Kosmider O Vacuoles in bone marrow progenitors: VEXAS syndrome and beyond Lancet Haematol 11 2 2024 e160 e167 38302223 10.1016/S2352-3026(23)00375-7

39 Lacombe V Prevost M Bouvier A Vacuoles in neutrophil precursors in VEXAS syndrome: diagnostic performances and threshold Br J Haematol 195 2 2021 286 289 34340250 10.1111/bjh.17679

40 De Almeida Braga C Bauvais M Sujobert P Deep learning-based blood abnormalities detection as a tool for VEXAS syndrome screening Int J Lab Hematol 47 1 2025 120 129 39275905 10.1111/ijlh.14368

41 Baggio C Oliviero F Padoan R Expanding the VEXAS diagnostic workup: the role of peripheral blood cytological analysis Front Immunol 15 2024 1466720 10.3389/fimmu.2024.1466720 PMC11484077 39421750

42 Patel N Dulau-Florea A Calvo KR Characteristic bone marrow findings in patients with UBA1 somatic mutations and VEXAS syndrome Semin Hematol 58 4 2021 204 211 34802541 10.1053/j.seminhematol.2021.10.007

43 Gurnari C Pagliuca S Durkin L Vacuolization of hematopoietic precursors: an enigma with multiple etiologies Blood 137 26 2021 3685 3689 33690844 10.1182/blood.2021010811 PMC8462399

44 Cherniawsky H Friedmann J Nicolson H VEXAS syndrome: a review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation Eur J Haematol 110 6 2023 633 638 36788756 10.1111/ejh.13944

45 Kanagal-Shamanna R Beck DB Calvo KR Clonal hematopoiesis, inflammation, and hematologic malignancy Annu Rev Pathol 19 2024 479 506 37832948 10.1146/annurev-pathmechdis-051222-122724

46 Arber DA Orazi A Hasserjian RP International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data Blood 140 11 2022 1200 1228 35767897 10.1182/blood.2022015850 PMC9479031

47 Khoury JD Solary E Abla O The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms Leukemia 36 7 2022 1703 1719 35732831 10.1038/s41375-022-01613-1 PMC9252913

48 Bernard E Tuechler H Greenberg PL Molecular International Prognostic Scoring System for myelodysplastic syndromes NEJM Evid 1 7 2022 EVIDoa2200008 10.1056/EVIDoa2200008 38319256

49 Steensma DP Dysplasia has A differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors Curr Hematol Malig Rep 7 4 2012 310 320 23015360 10.1007/s11899-012-0140-3

50 Kanagal-Shamanna R Loghavi S DiNardo CD Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation Haematologica 102 10 2017 1661 1670 28659335 10.3324/haematol.2017.167726 PMC5622850

51 Fleming MD Congenital sideroblastic anemias: iron and heme lost in mitochondrial translation Hematology 2011 1 2011 525 531 22160084 10.1182/asheducation-2011.1.525

52 Lindsley RC Mar BG Mazzola E Acute myeloid leukemia ontogeny is defined by distinct somatic mutations Blood 125 9 2015 1367 1376 25550361 10.1182/blood-2014-11-610543 PMC4342352

53 Greenberg PL Tuechler H Schanz J Revised International Prognostic Scoring System for myelodysplastic syndromes Blood 120 12 2012 2454 2465 22740453 10.1182/blood-2012-03-420489 PMC4425443

54 Zhao L-P Kosmider O Heiblig M Characteristics and prognostic significance of myelodysplasia-related features in VEXAS syndrome Leukemia 40 3 2026 661 665 41545701 10.1038/s41375-025-02858-2

55 Battipaglia G Vincenzi A Falconi G New scenarios in vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS) syndrome: evolution from myelodysplastic syndrome to acute myeloid leukemia Curr Res Transl Med 71 2 2023 103386 10.1016/j.retram.2023.103386 36905702

56 Sofi FA Naqati SM Ahmad M Bindroo M VEXAS syndrome presenting as diffuse alveolar haemorrhage BMJ Case Rep 17 3 2024 e259474 10.1136/bcr-2023-259474 PMC10982693 38538102

57 Diral E Campochiaro C Tomelleri A Case report: cytopenias in VEXAS syndrome - a WHO 2022 based approach in a single-center cohort Front Immunol 15 2024 1354130 10.3389/fimmu.2024.1354130 PMC10850384 38333211

58 Rudelius M Weinberg OK Niemeyer CM Shimamura A Calvo KR The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia Virchows Arch 482 1 2023 113 130 36445482 10.1007/s00428-022-03447-9

59 Steensma DP Patnaik MM Azacitidine as therapy for VEXAS syndrome Blood 146 12 2025 1380 1382 40965941 10.1182/blood.2025029732

60 Mekinian A Zhao LP Chevret S A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune/inflammatory disorders and VEXAS syndrome associated with MDS and CMML Leukemia 36 11 2022 2739 2742 36104395 10.1038/s41375-022-01698-8

61 Aalbers AM van Daele PLA Dalm V Valk PJM Raaijmakers M Long-term genetic and clinical remissions after cessation of azacitidine treatment in patients with VEXAS syndrome Hemasphere 8 8 2024 e129 10.1002/hem3.129 PMC11287193 39081801

62 Sockel K Götze K Ganster C VEXAS syndrome: complete molecular remission after hypomethylating therapy Ann Hematol 103 3 2024 993 997 38214707 10.1007/s00277-023-05611-w PMC10866742

63 Hadjadj J Nguyen Y Mouloudj D FRENVEX Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX Ann Rheum Dis 83 10 2024 1358 1367 38777378 10.1136/ard-2024-225640

64 Kunimoto H Miura A Maeda A Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome Int J Hematol 118 4 2023 494 502 37062784 10.1007/s12185-023-03598-8

65 Heiblig M Jachiet V Hadjadj J FRENVEX Group Efficacy of erythroid-stimulating agent and luspatercept in VEXAS syndrome: a multicenter retrospective study by the FRENVEX group Hemasphere 9 6 2025 e70156 10.1002/hem3.70156 PMC12131197 40469482

66 Malcovati L VEXAS: walking on the edge of malignancy Blood 142 3 2023 214 215 37471107 10.1182/blood.2023020772

67 Matsumoto H Fujita Y Fukatsu M Case report: coexistence of multiple myeloma and auricular chondritis in VEXAS syndrome Front Immunol 13 2022 897722 10.3389/fimmu.2022.897722 PMC9218563 35757758

68 Djerbi N Zimmermann K Roncador M Becker MO Manz MG Balabanov S Intrapatient competition of VEXAS syndrome and CML clones Blood Adv 7 22 2023 6815 6818 37738165 10.1182/bloodadvances.2023010814 PMC10679802

69 Austestad J Madland TM Sandnes M Haslerud TM Benneche A Reikvam H VEXAS syndrome in a patient with myeloproliferative neoplasia Case Rep Hematol 2023 2023 6551544 10.1155/2023/6551544 PMC9985496 36879894

70 Neupane K Jayarangaiah A Zhang Y Kumar A VEXAS syndrome with progression of MDS to MDS/MPN overlap syndrome BMJ Case Rep 15 12 2022 e251089 10.1136/bcr-2022-251089 PMC9791449 36549759

Acknowledgments

This research was supported by the 10.13039/100030692 Intramural Research Program of the 10.13039/100000002 National Institutes of Health (NIH).

M.M.P. acknowledges funding from the 10.13039/100000054 National Cancer Institute grant R01 CA272496.

The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services.

Authorship

Contribution: B.A.P., K.R.C., K.K.R., and M.M.P. conceptualized and wrote the manuscript; and K.R.C. and K.K.R. provided the hematopathology images.