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T-Cell Lymphoma With Sarcoid-Like Reaction and Secondary Myelofibrosis: A Unique Case Report and Literature Review.

INTRODUCTION: T-cell lymphomas are rare, comprising 10%-15% of non-Hodgkin lymphomas (NHLs). Their etiology remains unclear, and pathophysiology varies widely among subtypes. Sarcoid-like reactions (SLRs) have been reported in approximately 7.3% of NHLs, including T-cell lymphomas, and can closely resemble sarcoidosis clinically/histologically. This overlap complicates diagnosis, particularly when secondary myelofibrosis-a rare and poorly understood complication-arises. Myelofibrosis has also been observed in sarcoidosis, further blurring the distinction between these entities. Treatment for T

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… Nomenclature Tumor necrosis factor‐alpha Sarcoid‐like reaction Sarcoidosis‐lymphoma syndrome Ebstein–Barr virus Myeloproliferative neoplasm Janus Kinase‐2 Calreticulin Myeloproliferative leukemia virus Brentuximab vedotin combined with cyclophosphamide, doxorubicin, and prednisone Cyclophosphamide …

Tales from the Jazz ASH: highlights from the 2013 American Society of Haematology meeting.

The 55th annual ASH meeting was held in pleasant New Orleans and was the largest in its history, with 22,495 participants coming from 113 nations. A 'bench-to-bedside and back' attitude characterises haematology probably more than any other discipline in medicine and, as usual, this was reflected in the extremely wide breadth of the topics covered, including the last results from clinical trials and cutting-edge advancements in basic science. This year, the balance was arguably skewed: few truly clinical practice-changing results were presented. On the other hand, a great number of basic and t

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… Two groups independently came to the same finding, one headed by Tony Green in Cambridge (Jyoti et al ) and the other by Robert Kralovics in Vienna (Klampfl et al ): the protein chaperone calreticulin is the culprit, being mutated in the majority (70%–90%) of patients with wild-type JAK2 MPNs, in particular …

Understanding Aberrant Signaling to Elude Therapy Escape Mechanisms in Myeloproliferative Neoplasms.

Aberrant signaling in myeloproliferative neoplasms may arise from alterations in genes coding for signal transduction proteins or epigenetic regulators. Both mutated and normal cells cooperate, altering fragile balances in bone marrow niches and fueling persistent inflammation through paracrine or systemic signals. Despite the hopes placed in targeted therapies, myeloid proliferative neoplasms remain incurable diseases in patients not eligible for stem cell transplantation. Due to the emergence of drug resistance, patient management is often very difficult in the long term. Unexpected connecti

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… Since 2005, starting with the description of the Janus kinase 2 mutation (JAK2V617F) [ 1 , 2 ] followed by the discovery of myeloproliferative leukemia virus oncogene ( MPL ) [ 3 ] and calreticulin ( CALR ) mutations [ 4 , 5 ], the mutational landscape of MPNs has expanded enormously. … Somatic mutations of calreticulin in myeloproliferative neoplasms N. Engl. J. Med. 2013 369 2379 2390 10.1056/NEJMoa1311347 24325356 5. Nangalia J. Massie C.E. Baxter E.J. Nice F.L. Gundem G. Wedge D.C. Avezov E. Li J. Kollmann K. Kent D.G. …

Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.

X-box binding protein 1 (XBP1) is a member of the CREB/ATF basic region leucine zipper family transcribed as the unspliced isoform (XBP1-u), which, upon exposure to endoplasmic reticulum stress, is spliced into its spliced isoform (XBP1-s). XBP1-s interacts with the cAMP response element of major histocompatibility complex class II gene and plays critical role in unfolded protein response (UPR) by regulating the transcriptional activity of genes involved in UPR. XBP1-s is also involved in other physiological pathways, including lipid metabolism, insulin metabolism, and differentiation of immun

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… disintegrin and metalloproteinase 10 (ADAM10) , Krüppel-like factor 9 ( KLF9 ), and basic helix–loop–helix family member a15 ( BHLHA15 , also known as MIST1 ) [ 22 , 23 , 24 ]; while its binding to ERSE induces the transcription of ER chaperones such as glucose regulated protein 94 (GRP94), BiP, and calreticulin … apparatus, where it is cleaved by the proteasome of site-1 protease (S1P) and site-2 protease (S2P), releasing its N-terminal fraction (ATF6 p50), which functions as a transcription factor regulating heat shock protein family A member 5(Hspa5), heat shock protein 90 β family member 1(Hsp90b1), and calreticulin …

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel

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… Notably, ENPDOX treatment resulted in increased surface calreticulin exposure, HMGB1 secretion, and ATP release, which are hallmarks of chemotherapy-induced immunogenic cell death. …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… This leads to enhanced ICD in vitro with increased release of HMGB1 and ATP and increased levels of calreticulin on the cell surface. In a rat syngeneic tumor model, the fusion gene expression increased abscopal uninjected tumor responses [ 119 ]. … CVA21 also induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by ICD determinants calreticulin and release of HMGB1. Vaccination of mice with syngeneic MB49 bladder cancer cells undergoing CVA21 induced ICD induced in these mice the ability to reject MB49 tumors [ 129 ]. …

Nanomedicine and Onco-Immunotherapy: From the Bench to Bedside to Biomarkers.

The broad relationship between the immune system and cancer is opening a new hallmark to explore for nanomedicine. Here, all the common and synergy points between both areas are reviewed and described, and the recent approaches which show the progress from the bench to the beside to biomarkers developed in nanomedicine and onco-immunotherapy.

Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study.

AbstractPrevious studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and se

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… Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population. Blood. 2019;134(5):469–479. doi: 10.1182/blood.2019001113. 26. Christensen SF, Svingel LS, Kjaersgaard A, et al. …

Integration of multiparameter flow cytometry score improves prognostic stratification provided by standard models in primary myelofibrosis.

Prognostic modeling in myelofibrosis (MF) has classically pursued the integration of informative clinical and hematological parameters to separate patients' categories with different outcomes. Modern stratification includes also genetic data from karyotype and mutations. However, some poorly standardized variables, as peripheral blood (PB) blast count by morphology, are still included. In this study, we used multiparameter flow cytometry (MFC) with the aim of improving performance of existing scores. We studied 363 MF patients with available MFC files for PB CD34+ cells count determination at

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… Type 1 vs. type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia. 2014;28(7):1568‐1570. doi: 10.1038/leu.2014.83 20. Willatt L, Morgan SM. …

Natural products as metabolic modulators to enhance cancer immunotherapy: reprogramming the tumor microenvironment.

Cancer remains a major global health challenge, and although immunotherapy has achieved remarkable breakthroughs, its efficacy is often limited by tumor-induced immunosuppression within the tumor microenvironment (TME). Emerging evidence indicates that metabolic reprogramming plays a pivotal role in shaping the TME and regulating antitumor immune responses. Targeting tumor and immune cell metabolism has therefore become a promising strategy to enhance the effectiveness of cancer immunotherapy. This review first summarizes the metabolic reprogramming that occurs within the TME, including altera

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… A growing number of natural compounds have been shown to induce immunogenic cell death (ICD), a process characterized by the exposure or release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), high-mobility group box 1 (HMGB1), and heat shock proteins (HSPs) ( 138 ). … Compounds such as capsaicin ( 139 , 140 ), ginsenoside Rg3 ( 140 ), resveratrol ( 141 ), and the combination of quercetin with alantolactone ( 142 )can trigger ICD by promoting the exposure or release of DAMPs, including calreticulin, heat shock proteins, and HMGB1. …

Recombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives.

About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntr

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… Somatic mutations of calreticulin in myeloproliferative neoplasms. N. Engl. J. Med. 2013;369:2379–2390. doi: 10.1056/NEJMoa1311347. 10. Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., Avezov E., Li J., Kollmann K., Kent D.G. … From Janus kinase 2 to calreticulin: The clinically relevant genomic landscape of myeloproliferative neoplasms. Blood. 2014;123:3714–3719. doi: 10.1182/blood-2014-03-530865. 12. Skov V. Next Generation Sequencing in MPNs. …

T-Regulatory Cells In Tumor Progression And Therapy.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic ef

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… to be an effective chemotherapeutic agent or an adjuvant. 107 Mitoxantrone Mitoxantrone is a DNA binding anthracenedione that binds to deoxyribose sugar leading to a strand break. 122 Another marked effect of mitoxantrone, which augments anti-cancer immunity, is through cell surface expression of calreticulin … Calreticulin exposure dictates the immunogenicity of cancer cell death . Nat Med . 2007 ; 13 : 54 – 61 . doi: 10.1038/nm1523 17187072 124. Polanczyk MJ , Hopke C , Vandenbark AA , et al. …

A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma.

Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patien

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… Chao MP , Jaiswal S , Weissman-Tsukamoto R Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47 . Sci. Transl. Med. 2 ( 63 ), 63ra94 ( 2010 ). 10.1126/scitranslmed.3001375 PMC4126904 21178137 12. …

Overcoming resistance to immune checkpoint inhibitor therapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by molecular, immunological, and clinical heterogeneity and this has been reflected with changing paradigms in the treatment landscape of AML in recent years. Despite high remission rates with conventional chemotherapy regimens, most patients eventually relapse and have disappointing outcomes in the relapsed setting, with estimated 5-year overall survival rates ranging from 10-15%. Immune checkpoint inhibitors (ICIs) restrain T-cell suppressive signals delivered through cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death p

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… Chao et al. identified calreticulin as a key pro-apoptotic signal that enhances phagocytosis in cancer cells ( 90 ). … Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47 . Sci Trans Med . ( 2010 ) 2 : 63ra94–4 . doi: 10.1126/scitranslmed.3001375 , PMID: 21178137 PMC4126904 91 Zhao XW van Beek EM Schornagel K Van der Maaden H Van Houdt M Otten MA . …

Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress

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… Beyond maturation inhibition, disrupted phosphatidylserine exposure and delayed calreticulin translocation (synchronized with membrane rupture) reduce phagocytic efficiency. … As the process continues, transient calreticulin (CRT) exposure and ATP release occur during an intermediate phase, though immunogenicity remains limited. …

Acquired platelet disorders.

Platelets are essential to primary hemostasis, and defects in their number or function can lead to clinically significant bleeding or thrombosis. Acquired platelet disorders are far more common than the inherited forms and arise in a wide range of settings, including drug exposure, autoimmune, systemic, and critical illnesses. This review examines current understanding of the mechanisms driving acquired platelet dysfunction and outlines the diagnostic and therapeutic approaches that are shaping contemporary standards of care. Drug-related and immune-mediated platelet defects remain the most re

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… ADAMTS13, a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13; aPTT, activated partial thromboplastin time; BCR::ABL1, BCR–ABL1 fusion (Philadelphia chromosome); BM, bone marrow; CALR, calreticulin; CBC, complete blood count; Dx, diagnosis; EM, electron microscopy; GP, Glycoprotein … Platelet function studies in myeloproliferative neoplasms patients with Calreticulin or JAK2 (V617F) mutation. Res Pract Thromb Haemost. (2023) 7:100060. doi: 10.1016/j.rpth.2023.100060, PMID: 55. Altahan R, Bourguignon A, Tasneem S, Hayward CPM. …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

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… AgNPs-G would lose the ability to trigger calreticulin exposure and HSP70 release, reducing cytotoxicity in breast cancer. AgAu NPs would not effectively promote apoptosis or HCT116 cell death without HSP70. Ag 2 S NDs would show reduced photothermal therapy efficacy, hindering tumour ablation. … AgNPs-G treatment triggers calreticulin exposure and HSP70 release | In vivo, AgNPs-G vaccination reduces tumour weight and enhances mouse survival, highlighting potential therapeutic impact on cancer through HSP70 | [ 115 ] AgAu NPs | All types of cancer | AgAu NPs induce dose-dependent cytotoxicity …

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

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… Over 95% of PV, ET, and PMF are associated with mutually exclusive somatic driver mutations JAK2 V617F, calreticulin ( CALR ), and myeloproliferative leukemia protein ( MPL ) [ 9 , 10 , 11 , 12 , 13 ]. Acquisition of somatic driver mutations leads to the development of the MPN stem cells. …

Risks of Solid and Lymphoid Malignancies in Patients with Myeloproliferative Neoplasms: Clinical Implications.

In the past decade, several studies have reported that patients with chronic myeloproliferative neoplasms (MPNs) have an increased risk of second solid cancer or lymphoid hematological cancer. In this qualitative review study, we present results from studies that report on these cancer risks in comparison to cancer incidences in the general population or a control group. Our literature search identified 12 such studies published in the period 2009-2018 including analysis of more than 65,000 patients. The results showed that risk of solid cancer is 1.5- to 3.0-fold elevated and the risk of lymp

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… Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population Blood 2019 134 469 479 10.1182/blood.2019001113 31217187 42. Pedersen K.M. Colak Y. Hasselbalch H.C. Ellervik C. Nordestgaard B.G. Bojesen S.E. …

Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation.

BackgroundCytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms.MethodsThis study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters.ResultsThe proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JA

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… Nearly 10–15% of ET, PMF, and PV patients progress to acute myeloid leukemia. 1 , 2 Constitutive activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway due to acquired somatic mutations in the JAK2 , calreticulin or MPL genes may drive the course …