title: Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.
abstract: 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.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Leiwen
authors.initials: L
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Rao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huai
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Yirui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Mi
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China wangjx@ihcams.ac.cn.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D011839:Radiation, Ionizing; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53
keywords: HSC; antiapoptosis; self-renewal; transgenic