Phenotypic characterization of malignant progenitor cells in patients with idiopathic myelofibrosis

• Main Authors: Yonghua Bao, Wenyang Hu, Yongchen Guo, Wancai Yang
• Format: Article
• Language: English
• Published: Elsevier 2019-09-01
• Series: Hematology/Oncology and Stem Cell Therapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S1658387619300020

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. Keywords: Chromosome abnormality, Idiopathic myelofibrosis, IL3-Rα, JAK2V617F