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Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways.
MedLine Citation:
PMID:  23391335     Owner:  NLM     Status:  Publisher    
All-trans retinoic acid (ATRA) induces clinical remission in most acute promyelocytic leukemia (APL) patients by inducing terminal differentiation of APL cells toward mature granulocytes. Here we report that human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are capable of inducing granulocytic differentiation of APL-derived NB4 cell line as well as primary APL cells and also cooperate with ATRA in an additive manner. Transwell co-culture experiments revealed that UC-MSCs' differentiation-inducing effect was mediated through some soluble factors. Differentiation attenuation by IL-6Ra neutralization and induction by addition of exogenous IL-6 confirmed that IL-6 secreted by UC-MSCs was at least partially responsible for this differentiation induction process. Moreover, we found that UC-MSCs activated MEK/ERK signaling pathway in promyelocytic cells and pharmacological inhibition of MEK/ERK pathway reversed UC-MSCs-induced differentiation, indicating that UC-MSCs exerted effect through activation of MEK/ERK signaling pathway. These results demonstrate for the first time a stimulatory effect of MSCs on the differentiation of APL cells and bring a new insight into the interaction between MSCs and leukemic cells. Our data suggest that UC-MSCs/ATRA combination could be used as a novel therapeutic strategy for APL patients.
Fang Chen; Kang Zhou; Lei Zhang; Fengxia Ma; Dandan Chen; Junjie Cui; Xiaoming Feng; Shaoguang Yang; Ying Chi; Zhi-Bo Han; Feng Xue; Lijuan Rong; Meili Ge; Li Wan; Shuxia Xu; Wenjing Du; Shihong Lu; Hongying Ren; Zongchao Han
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-7
Journal Detail:
Title:  Stem cells and development     Volume:  -     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Hematology and Blood Diseases Hospital, Tianjin, Tianjin, China;
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