High mobility group Box-1 inhibits cancer cell motility and metastasis by suppressing activation of transcription factor CREB and nWASP expression.

UNLABELLED: Core Binding Factor Acute Myeloid Leukemia (CBF-AML), defined by RUNX1::RUNX1T1 or CBFB::MYH11 fusions, represents a biologically favorable AML subtype. The Indian data-especially under WHO 2022 criteria-are limited. This study analyzed the demographic, morphological, and immunophenotypic spectrum of CBF-AML in a large North Indian cohort, focusing on pediatric-adult differences, low-blast presentations, and immunophenotypic signatures.An ambispective study (2017-2024) of 196 genetically confirmed CBF-AML cases included clinical, hematopathological, and flow cytometric evaluation. Statistical comparisons were performed using appropriate tests. CBF-AML constituted 16.4% of all AML cases, more frequent in pediatric (44.2%) than adults (11.1%). RUNX1::RUNX1T1 accounted for 85.7% and CBFB::MYH11 for 14.3%. Age-stratified analysis showed higher rates of lymphadenopathy, hepatomegaly, and splenomegaly in CBFB::MYH11 patients aged 41-60 years (p < 0.05). Extramedullary disease occurred in 11.2%. Sixteen patients (8.2%) had <20% marrow blasts, often mimicking myelodysplastic/myeloproliferative neoplasms (MDS/MPN), underscoring the need for molecular testing irrespective of blast count. Morphologically, CBFB::MYH11 was associated with myelomonocytic features and eosinophilia; RUNX1::RUNX1T1 showed dysgranulopoiesis and long slender Auer rods. Immunophenotyping revealed CD123 and CD86 overexpression in CBFB::MYH11 (90% and 83.3%, respectively) besides higher expression of monocytic markers. RUNX1::RUNX1T1 showed frequent CD19, CD22, and CD56 expression. Survival analysis limited to a small treated subset (n = 30), revealed complete remission rate of 76.7% following induction, with median overall and relapse-free survival of 408 and 215 days, respectively. This largest single-center Indian series of CBF-AML in the WHO 2022 era highlights subtype-specific clinicopathological patterns, reaffirms classic morphology, and emphasizes routine molecular testing, particularly in low-blast or atypical presentations. Overexpression of CD123 and CD86 in CBFB::MYH11 may have diagnostic and therapeutic relevance.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12288-025-02150-4.