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Oncogene iASPP enhances self‐renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation
Author(s) -
Jia Yujiao,
Peng Leiwen,
Rao Qing,
Xing Haiyan,
Huai Lei,
Yu Pei,
Chen Yirui,
Wang Cuicui,
Wang Min,
Mi Yingchang,
Wang Jianxiang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-244632
Subject(s) - haematopoiesis , apoptosis , progenitor cell , stem cell , biology , cancer research , hematopoietic stem cell , transgene , oncogene , myeloid leukemia , myeloid , microbiology and biotechnology , cell cycle , gene , genetics
iASPP is a member of the apoptosis‐stimulating proteins of p53 (ASPP) family and negatively regulates the apoptotic function of p53. In a hematopoietic system, overexpression of iASPP results in blockage of apoptosis, which may play a role in regulating hematopoietic stem cell (HSC) numbers. To address this, we first analyzed the expression of iASPP in patients with acute leukemia (AL) and found it was highly expressed in patients with AL. We further established a transgenic mouse model in which human iASPP was specifically expressed in hematopoietic cells. Overexpression of iASPP led to an increase in the proportion of long‐term HSCs, short‐term HSCs, multipotent progenitors, and common myeloid progenitor. HSCs from iASPP transgenic mice had an advantage in long‐term reconstitution potential. In addition, the hematopoietic cells from iASPP transgenic mice exhibited a significantly lower level of p53 dependent apoptosis. After irradiation damage, hematopoietic cells of iASPP transgenic mice had a higher level of γ‐H2AX expression, which lasted for a longer time. These results provide the first evidence that the iASPP can increase HSC populations and reconstitution capacity. Interestingly, in response to cell damage stimuli, hematopoietic cells can be protected against apoptosis by iASPP; meanwhile these apoptosis‐resistant cells would have more mutation accumulation, which might be the potential risk for malignant transformation.—Jia, Y., Peng, L., Rao, Q., Xing, H., Huai, L., Yu, P., Chen, Y., Wang, C., Wang, M., Mi, Y., Wang, J. Oncogene iASPP enhances self‐renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation. FASEB J . 28, 2816–2827 (2014). www.fasebj.org