USP22 deficiency leads to myeloid leukemia upon oncogenic Kras activation through a PU.1-dependent mechanism.

Blood
Johanna Melo-CardenasDeyu Fang

Abstract

Ras mutations are commonly observed in juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML). JMML and CMML transform into acute myeloid leukemia (AML) in about 10% and 50% of patients, respectively. However, how additional events cooperate with Ras to promote this transformation are largely unknown. We show that absence of the ubiquitin-specific peptidase 22 (USP22), a component of the Spt-Ada-GCN5-acetyltransferase chromatin-remodeling complex that is linked to cancer progression, unexpectedly promotes AML transformation in mice expressing oncogenic KrasG12D/+ USP22 deficiency in KrasG12D/+ mice resulted in shorter survival compared with control mice. This was due to a block in myeloid cell differentiation leading to the generation of AML. This effect was cell autonomous because mice transplanted with USP22-deficient KrasG12D/+ cells developed an aggressive disease and died rapidly. The transcriptome profile of USP22-deficient KrasG12D/+ progenitors resembled leukemic stem cells and was highly correlated with genes associated with poor prognosis in AML. We show that USP22 functions as a PU.1 deubiquitylase by positively regulating its protein stability and promoting the expression of PU.1 target g...Continue Reading

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Citations

May 28, 2019·Journal of Biomedical Science·Ming-Jer YoungJan-Jong Hung
Sep 19, 2019·Cell Death and Differentiation·Robyn Laura KosinskySteven A Johnsen
Feb 19, 2020·The Journal of Experimental Medicine·Yana ZhangDeyu Fang
Jun 6, 2020·Nature·Jessica T CortezDeyu Fang
Jul 31, 2020·World Journal of Clinical Oncology·Mónica T FernandesJosé Bragança
Feb 26, 2020·Cancer Research·Lisa Maria MustachioSharon Y R Dent
Aug 27, 2019·Biochimica Et Biophysica Acta. Reviews on Cancer·Ji ChengWenyi Wei
Jan 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoli HuXueqiong Zhu
Nov 15, 2020·Molecular Cancer Research : MCR·Mukul MishraArun Kumar Trivedi
Mar 7, 2020·Trends in Immunology·Blanca T Gutierrez-DiazPanagiotis Ntziachristos
Mar 10, 2021·Bulletin du cancer·Sa ZhouTongcun Zhang
May 15, 2021·Cancer Letters·Tingting FengXiao Xu
Jun 3, 2021·International Journal of Molecular Sciences·Charles Ducker, Peter E Shaw
Aug 30, 2021·Biomarker Research·Hu LeiYingli Wu

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