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Role of Flow Cytometric Enumeration of Circulating hMICL ( CD371 ) Positive Leukemic Stem Cells in Diagnosis and Prognostication of BCR :: ABL1 ‐Negative Myeloproliferative Neoplasms

Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT Background BCR‐ABL1‐negative myeloproliferative neoplasms (MPNs) often exhibit overlapping clinical and morphological features, making accurate subcategorization challenging. The h‐MICL (CD371) antigen, selectively expressed on leukemic stem cells (LSCs) and absent on CD34 + CD38 − cells in normal or regenerating marrow, represents a potential diagnostic and prognostic marker. Objectives This study aimed to evaluate the diagnostic utility of circulating CD34 + CD38 − h‐MICL + cells in subtyping BCR‐ABL1‐negative MPNs and to assess their correlation with the Dynamic International Prognostic Scoring System (DIPSS) score. Additionally, to identify a cut‐off value of CD34 + CD38 − h‐MICL + cells that can effectively differentiate PMF. Methods Fifty‐four patients with BCR‐ABL1‐negative MPNs were prospectively enrolled at a tertiary care center in North India over 18 months. Peripheral blood was analyzed via flow cytometry to quantify CD34 + , CD34 + CD38 + , CD34 + CD38 − , and CD34 + CD38 − h‐MICL + cell subsets. Results A significant increase in circulating CD34 + CD38 − h‐MICL + cells was observed in patients with overt MF (median 2.8%), prefibrotic MF (4.15%), and post‐PV/ET MF (3%) compared to PV and ET (median 0%; p < 0.001). A threshold of ≥ 0.9% CD34 + CD38 − h‐MICL + cells effectively identified MF cases with 88% sensitivity and 89% specificity. Moreover, a positive correlation was found between the percentage of CD34 + CD38 − h‐MICL + cells and DIPSS score ( ρ = 0.41, p = 0.036), with every 1.72% increase in this cell population corresponding to a 1‐point rise in DIPSS score. Conclusion Circulating CD34 + CD38 − h‐MICL + cells represent a promising biomarker; their quantification may aid in subclassification, particularly in distinguishing prefibrotic MF from ET, and may serve as a potential target for future therapeutic strategies. Further validation in larger cohorts is warranted.
Language: English
Subfield: Genetics
Field: Medicine
Open Access status: green
OpenAlex ID: W7159593496
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