PMID- 30796884 OWN - NLM STAT- MEDLINE DCOM- 20200504 LR - 20200504 IS - 2589-0646 (Electronic) IS - 2589-0646 (Linking) VI - 12 IP - 3 DP - 2019 Sep TI - Phenotypic characterization of malignant progenitor cells in patients with idiopathic myelofibrosis. PG - 146-154 LID - S1658-3876(19)30002-0 [pii] LID - 10.1016/j.hemonc.2019.01.001 [doi] AB - 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-3Ralpha/CD123 labeling and further characterized them by genetic and functional analyses. RESULTS: We differentiated IM PB CD34(+) cells into three subpopulations (IL-3Ralpha(high), IL-3Ralpha(low), and IL-3Ralpha(negative)). IL-3Ralpha(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-3Ralpha(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-3Ralpha(high) CD34(+) cells exhibited abnormal colony forming ability and carried greater percentage of JAK2V617F mutant allele compared with IL-3Ralpha(low) and IL-3Ralpha(negative) CD34(+) cells. CONCLUSION: These data indicate that IL-3Ralpha(high) CD34(+) cells from IM enriched for the malignant progenitor cells and IL-3Ralpha/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. CI - Copyright (c) 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved. FAU - Bao, Yonghua AU - Bao Y AD - Department of Pathology, Institute of Precision Medicine, Jining Medical University, Jining, China. Electronic address: baoyonghua2005@126.com. FAU - Hu, Wenyang AU - Hu W AD - Department of Pathology, Institute of Precision Medicine, Jining Medical University, Jining, China. Electronic address: wyhu02@yahoo.com. FAU - Guo, Yongchen AU - Guo Y AD - Department of Pathology, Institute of Precision Medicine, Jining Medical University, Jining, China. FAU - Yang, Wancai AU - Yang W AD - Department of Pathology, Institute of Precision Medicine, Jining Medical University, Jining, China. LA - eng PT - Journal Article DEP - 20190220 PL - Saudi Arabia TA - Hematol Oncol Stem Cell Ther JT - Hematology/oncology and stem cell therapy JID - 101468532 RN - 0 (Antigens, CD34) RN - 0 (IL3RA protein, human) RN - 0 (Interleukin-3 Receptor alpha Subunit) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Antigens, CD34/analysis/genetics MH - Cells, Cultured MH - Chromosome Aberrations MH - Hematopoietic Stem Cells/metabolism/*pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Interleukin-3 Receptor alpha Subunit/analysis/genetics MH - Janus Kinase 2/genetics MH - Neoplastic Stem Cells/metabolism/pathology MH - Point Mutation MH - Primary Myelofibrosis/genetics/*pathology OTO - NOTNLM OT - Chromosome abnormality OT - IL3-Ralpha OT - Idiopathic myelofibrosis OT - JAK2V617F EDAT- 2019/02/24 06:00 MHDA- 2020/05/05 06:00 CRDT- 2019/02/24 06:00 PHST- 2018/08/16 00:00 [received] PHST- 2019/01/07 00:00 [revised] PHST- 2019/01/21 00:00 [accepted] PHST- 2019/02/24 06:00 [pubmed] PHST- 2020/05/05 06:00 [medline] PHST- 2019/02/24 06:00 [entrez] AID - S1658-3876(19)30002-0 [pii] AID - 10.1016/j.hemonc.2019.01.001 [doi] PST - ppublish SO - Hematol Oncol Stem Cell Ther. 2019 Sep;12(3):146-154. doi: 10.1016/j.hemonc.2019.01.001. Epub 2019 Feb 20.