Phenotypic characterization of malignant progenitor cells in patients with idiopathic myelofibrosis

Idiopathic myelofibrosis (IM) is a clonal hematological malignancy originating from pluripotent hematopoietic stem cells (HSC). HSC are very rare potent cells that reside in the bone marrow (BM) and at a lower level in peripheral blood (PB). Previous studies showed that IM PB CD34⁺ cells contain not only BM repopulating cells belonging to the malignant clone but also residual normal HSC.

In the current study, we separated the subpopulations of IM PB CD34⁺ cells using IL-3Rα/CD123 labeling and further characterized them by genetic and functional analyses.

We differentiated IM PB CD34⁺ cells into three subpopulations (IL-3Rα^high, IL-3Rα^low, and IL-3Rα^negative). IL-3Rα^high CD34⁺ cell subgroup represents a small population in IM PB CD34⁺ cells which was not seen in normal G-CSF mobilized CD34⁺ cells. IM IL-3Rα^high CD34⁺ cells contained significant higher percentage of cells bearing marker chromosome detected by fluorescence in situ hybridization (FISH) analysis. In the absence of growth factors, IM IL-3Rα^high CD34⁺ cells exhibited abnormal colony forming ability and carried greater percentage of JAK2V617F mutant allele compared with IL-3Rα^low and IL-3Rα^negative CD34⁺ cells.

These data indicate that IL-3Rα^high CD34⁺ cells from IM enriched for the malignant progenitor cells and IL-3Rα/CD123 may be a potential biomarker and therapeutic target for IM. Our findings will be further validated in future studies with a larger sample size and serial transplant in murine models.