Friend or foe: Can activating mutations in NOTCH1 contribute to a favorable treatment outcome in patients with T-ALL?

Aviya Goldshtein, Michael Berger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Despite sig-nifcant improvement in the treatment of T-ALL, approximately 20% of children and most adults succumb to resistant or relapsed disease. Transformation events occur during crucial steps of thymocyte development and have been related to the expression of certain oncogenes such as TAL2, TLX1, LYL1, LMO1, and NOTCH1. Mutations that lead to constitutive activation of NOTCH1 are most commonly found in human patients with T-ALL. Moreover, overexpression of the intracellular portion of NOTCH1 can lead to the initiation of T-ALL in mouse models. These findings suggest that NOTCH1 may promote tu-morigenesis through the regulation of differentiation of leukemic cells, and, potentially, of leukemia-initiating cell identity and function. Multiple studies and clinical trials aimed at targeting NOTCH1 in T-ALL or using NOTCH1 mutations as a prognostic tool are currently underway. Recent studies unexpectedly found that activating mutations in NOTCH1 are correlated with better treatment outcome. Here we review these studies and discuss possible explanations for these findings.

Original languageAmerican English
Pages (from-to)399-404
Number of pages6
JournalCritical Reviews in Oncogenesis
Volume19
Issue number5
DOIs
StatePublished - 2014

Bibliographical note

Publisher Copyright:
© 2014 Begell House, Inc.

Keywords

  • NOTCH1
  • T-cell acute lymphoblastic leukemia (T-ALL)
  • leukemia-initiating cells (LICs)

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