The molecular basis of T cell acute lymphoblastic leukemia

Abstract

T cell acute lymphoblastic leukemias (T-ALLs) arise from the malignant transformation of hematopoietic progenitors primed toward T cell development, as result of a multistep oncogenic process involving constitutive activation of NOTCH signaling and genetic alterations in transcription factors, signaling oncogenes, and tumor suppressors. Notably, these genetic alterations define distinct molecular groups of T-ALL with specific gene expression signatures and clinicobiological features. This review summarizes recent advances in our understanding of the molecular genetics of T-ALL.

Promising New Strategies to Target Gene Regulatory Factors in T-Cell Acute Lymphoblastic Leukemia

“…Recent and ongoing research continues to uncover many of the molecular and genetic aberrations that occur during thymocyte development that lead to leukemic transformation and progression. Many of these aberrant genetic events converge on transcriptional pathways, including the dysregulation of specific DNA-binding transcription factor genes including NOTCH1, TAL1, MYC, MYB, several of the HOX genes and others [2]. While these factors represent important targets for rationally directed therapies, direct chemical modulation of transcription factors is inherently difficult and often seen as intractable owing to the lack of 'druggable' protein domains.…”

Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in mice

“…Deregulated tyrosine kinase signaling was detected in human T cell acute lymphoblastic leukemia, but activating KIT mutations were not reported [41]. KIT is frequently expressed in early T cell precursor ALL, but this expression may reflect the immature cell origin rather than being linked to malignant transformation [42].…”

CD34 Positive Pediatric T Lymphoblastic Leukemia: A Tertiary Care Centre Experience

“…In particular, the activating mutations in the Notch pathways are believed to occur in a large proportion of human TALL. These findings on genetic events may open up new therapeutic possibilities (20) .CD34 positivity associated with poor survival is not explained by the mRNA expression levels of multidrug resistant genes (21) .Gene expression profiling studies have identified several gene expression signatures,some of which correspond to specific stages of thymocyte development (22). LYL1+ signature corresponds to pro-T stage,HOX11+ to early cortical stage, and TAL1+ to late cortical thymocyte stage (1,23) .…”