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

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.