期刊
ONCOGENE
卷 28, 期 23, 页码 2276-2288出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.87
关键词
PLZF; c-kit; hematopoietic progenitor cells; erythropoiesis
资金
- Italian Ministry of Health
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- 'Fondazione Roma', Rome, Italy
The promyelocytic leukemia zinc-finger protein (PLZF) is a transcription factor and c-kit is a receptor tyrosine kinase associated with human disease, particularly in hematopoietic cells. MicroRNAs (miRs) are post-transcriptional regulators of gene expression, and c-kit has been described as a target of miRs-221 and -222 in erythropoiesis. In the present study, we identified c-kit as a target of PLZF in normal and leukemic cells. Particularly, in erythropoietic (E) culture of CD34(+) progenitors, PLZF is downregulated, whereas c-kit expression at both the mRNA and protein levels inversely increases during the first days of E differentiation. In functional experiments, PLZF transfection induces c-kit downregulation, inhibits E proliferation and delays differentiation, whereas PLZF knockdown induces opposite effects, independently of miRs-221 and -222 expression. The inverse correlation between PLZF and c-kit expression was found in normal CD34(+)38(+/-) hematopoietic progenitor/stem cells and in acute myeloid leukemias of M0/M1 French-American-British subtypes, suggesting that the control of PLZF on c-kit expression may be crucial at the level of the stem cell/progenitor compartment. Altogether, our data indicate a new mechanism of regulation of c-kit expression that involves a transcriptional control by PLZF in CD34(+) cells and early erythropoiesis. Oncogene (2009) 28, 2276-2288; doi: 10.1038/onc.2009.87; published online 4 May 2009
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