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

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.