ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells.

Autor:	Yang S; Department of Pathophysiology, State Key Laboratory of Oncogenes and Related Genes, Chinese Academy of Medical Sciences Research Unit 2019RU043, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China., Zhu XN; Department of Pathophysiology, State Key Laboratory of Oncogenes and Related Genes, Chinese Academy of Medical Sciences Research Unit 2019RU043, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China., Zhang HL; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Yang Q; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Wei YS; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Zhu D; Department of Hematology, Ren-Ji Hospital, SJTU-SM, Shanghai, China., Liu MD; International Peace Maternity and Child Health Hospital, SJTU-SM, Shanghai, China; and., Shen SM; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Xia L; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., He P; Department of Pathophysiology, State Key Laboratory of Oncogenes and Related Genes, Chinese Academy of Medical Sciences Research Unit 2019RU043, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China., Ge MK; Department of Pathophysiology, State Key Laboratory of Oncogenes and Related Genes, Chinese Academy of Medical Sciences Research Unit 2019RU043, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China., Pan YL; International Peace Maternity and Child Health Hospital, SJTU-SM, Shanghai, China; and., Zhao M; Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Ministry of Education, Guangzhou, China., Wu YL; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Zheng JK; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China., Chen GQ; Department of Pathophysiology, State Key Laboratory of Oncogenes and Related Genes, Chinese Academy of Medical Sciences Research Unit 2019RU043, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China., Yu Y; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, SJTU-SM, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Dec 16; Vol. 138 (24), pp. 2485-2498.
DOI:	10.1182/blood.2020010400
Abstrakt:	Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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