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MYC in T-cell acute lymphoblastic leukemia: functional implications and targeted strategies.


ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that frequently occurs in children and adolescents, which results from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation of T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers. Mounting evidence highlights the critical role of the NOTCH1-MYC highway toward the initiation and progression of T-ALL. MYC has been emphasized as a primary NOTCH1 transcriptional target impinging in leukemia-initiating cell activity particularly responsible for disease onset and relapse. These findings lay a foundation of T-ALL as an ideal disease model for studying MYC-mediated cancer. The biology of MYC deregulation in T-ALL supports innovative strategies for therapeutic targeting of MYC. To summarize the relevant literature and data in recent years, we here provide a comprehensive overview of the functional importance of MYC in T-ALL development, and the molecular mechanisms underlying MYC deregulation in T-ALL. Finally, we illustrate the innovative MYC-targeted approaches that have been evaluated in pre-clinical models and shown significant efficacy. Given the complexity of T-ALL molecular pathogenesis, we propose that a combination of anti-MYC strategies with conventional chemotherapies or other targeted/immunotherapies may provide the most durable response, especially for those patients with relapsed and refractory T-ALL.

SUBMITTER: Li Q 

PROVIDER: S-EPMC8974894 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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MYC in T-cell acute lymphoblastic leukemia: functional implications and targeted strategies.

Li Qilong Q   Pan Sa S   Xie Ting T   Liu Hudan H  

Blood science (Baltimore, Md.) 20210607 3


T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that frequently occurs in children and adolescents, which results from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation of T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers. Mounting evidence highlights the critical role of the NOTCH1-MYC highway toward the initiation and progression of T-ALL. MYC has been emphasized as a primary NOTCH1 transcription  ...[more]

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