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OBJECTIVE/BACKGROUND 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. METHODS 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. RESULTS We differentiated IM PB CD34+ cells into three subpopulations (IL-3Rαhigh, IL-3Rαlow, and IL-3Rαnegative). IL-3Rαhigh 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-3Rαhigh 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-3Rαhigh CD34+ cells exhibited abnormal colony forming ability and carried greater percentage of JAK2V617F mutant allele compared with IL-3Rαlow and IL-3Rαnegative CD34+ cells. CONCLUSION These data indicate that IL-3Rαhigh 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.