PMID- 30123289 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2018 DP - 2018 TI - Alteration in the Cytokine Secretion of Bone Marrow Stromal Cells from Patients with Chronic Myelomonocytic Leukemia Contribute to Impaired Hematopoietic Supportive Activity. PG - 5921392 LID - 10.1155/2018/5921392 [doi] LID - 5921392 AB - Bone marrow stromal cells (BMSCs) represent an important cellular component of the bone marrow microenvironment, which play an important role in supporting and regulating the proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). We have previously reported that the ability of BMSCs derived from CMML patients (CMML-BMSCs) in supporting the expansion of cord blood (CB) CD34(+) cells was significantly reduced compared to BMSCs derived from healthy donors (HD-BMSCs). In addition, CMML-BMSCs led to a skewed differentiation of CB CD34(+) cells favoring myeloid lineage compared with HD-BMSCs. To assess whether the altered cytokine secretion was one of the mechanisms to mediate the impaired hematopoietic supportive activity of CMML-BMSCs, a transwell coculture followed by cytokine array was performed. We showed that noncontacted coculture with CMML-BMSCs preferentially promoted the differentiation of CB CD34(+) cells toward myeloid lineage. The expression levels of multiple cytokines (IL-6, IL-8, and GRO-beta) were markedly reduced in CMML-BMSCs compared with HD-BMSCs. By supplementing IL-6, IL-8, or GRO-beta, the hematopoietic supportive activity of CMML-BMSCs was partially restored. These results suggested that BMSCs may contribute to the pathogenesis of CMML by altering their cytokine secretion, which will shed light on the further investigation to develop novel therapeutic strategies for CMML patients. FAU - Shi, Hui AU - Shi H AUID- ORCID: 0000-0002-5819-1220 AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Wang, Yingshao AU - Wang Y AUID- ORCID: 0000-0002-1381-9985 AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Li, Rong AU - Li R AUID- ORCID: 0000-0002-1805-810X AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Xing, Wen AU - Xing W AUID- ORCID: 0000-0002-3380-3374 AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. FAU - Yang, Feng-Chun AU - Yang FC AD - Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. AD - Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA. FAU - Bai, Jie AU - Bai J AUID- ORCID: 0000-0002-7493-8347 AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. AD - Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin, China. FAU - Zhou, Yuan AU - Zhou Y AUID- ORCID: 0000-0003-4413-7490 AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. LA - eng PT - Journal Article DEP - 20180710 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC6079359 EDAT- 2018/08/21 06:00 MHDA- 2018/08/21 06:01 PMCR- 2018/07/10 CRDT- 2018/08/21 06:00 PHST- 2018/02/15 00:00 [received] PHST- 2018/05/03 00:00 [revised] PHST- 2018/05/15 00:00 [accepted] PHST- 2018/08/21 06:00 [entrez] PHST- 2018/08/21 06:00 [pubmed] PHST- 2018/08/21 06:01 [medline] PHST- 2018/07/10 00:00 [pmc-release] AID - 10.1155/2018/5921392 [doi] PST - epublish SO - Stem Cells Int. 2018 Jul 10;2018:5921392. doi: 10.1155/2018/5921392. eCollection 2018.