E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia

Frontiers in Immunology

Geoffrey Parriott²  Barbara L. Kee³ 

[1] Committee on Cancer Biology, University of Chicago, Chicago, IL, United States;Committee on Immunology, University of Chicago, Chicago, IL, United States;Department of Pathology, University of Chicago, Chicago, IL, United States;

关键词: Leukemia;    E protein;    TAL1;    LYL1;    murine;    T lymphocyte;   

DOI  :  10.3389/fimmu.2022.885144

来源: DOAJ

【 摘 要 】

T Lymphocyte Acute Lymphoblastic Leukemia (ALL) is an aggressive disease arising from transformation of T lymphocytes during their development. The mutation spectrum of T-ALL has revealed critical regulators of the growth and differentiation of normal and leukemic T lymphocytes. Approximately, 60% of T-ALLs show aberrant expression of the hematopoietic stem cell-associated helix-loop-helix transcription factors TAL1 and LYL1. TAL1 and LYL1 function in multiprotein complexes that regulate gene expression in T-ALL but they also antagonize the function of the E protein homodimers that are critical regulators of T cell development. Mice lacking E2A, or ectopically expressing TAL1, LYL1, or other inhibitors of E protein function in T cell progenitors, also succumb to an aggressive T-ALL-like disease highlighting that E proteins promote T cell development and suppress leukemogenesis. In this review, we discuss the role of E2A in T cell development and how alterations in E protein function underlie leukemogenesis. We focus on the role of TAL1 and LYL1 and the genes that are dysregulated in E2a-/- T cell progenitors that contribute to human T-ALL. These studies reveal novel mechanisms of transformation and provide insights into potential therapeutic targets for intervention in this disease.

【 授权许可】

Unknown