It's T-ALL about Notch

Demarest, Renée M.; Ratti, Francesca; Capobianco, Anthony J.

doi:10.1038/onc.2008.222

Cited by 100 publications

(102 citation statements)

References 81 publications

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“…Furthermore, the t(7;9)(q34;q34.3) translocation, which occurs in ~1% of T-ALL, leads to the constitutive expression of active Notch1. 7 Notch1 aberrations are found in association with other aberrations, consistent with their occurrence in immature cells, susceptible to additional hits.…”

Section: Lesions Involving Known Oncogenessupporting

confidence: 49%

T-cell acute lymphoblastic leukemia

Chiaretti¹,

Foà²

2009

Haematologica

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Section: Lesions Involving Known Oncogenessupporting

confidence: 49%

T-cell acute lymphoblastic leukemia

Chiaretti¹,

Foà²

2009

Haematologica

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“…29 More than half of the T-ALLs harbor Notch 1 mutations, which result in aberrant activation of this signaling pathway. 47 Targeted expression of the active form of Notch 1 to immature T cells in a zebrafish transgenic model resulted in the development of T-cell leukemias. 48 The presence of Notch mutations are counterintuitively predictive of good initial therapeutic responses, although not of outcome.…”

Section: Transcriptional Targets Of P53mentioning

confidence: 99%

p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies

2011

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The p53 tumor suppressor protein has a key role in the induction of apoptosis of chronic lymphocytic leukemia (CLL) cells. Abnormalities within the p53 pathway identify a subset of patients with a poor prognosis. This review describes recent advances in understanding the mechanisms that regulate p53 levels and the role of p53 in the control of the cell cycle and of apoptosis. The classical model of p53-mediated apoptosis emphasizes the transcriptional activation of proapoptotic genes. In contrast, a novel model emphasizes p53's non-transcriptional actions as the major route of apoptosis induction, whereas its transcriptional arm predominantly upregulates antiapoptotic genes, thus providing a negative feedback mechanism that limits apoptosis. Further studies have identified the Notch pathway as a candidate p53-induced antiapoptotic mechanism. In contrast to the classical model, the novel model predicts that pharmacological inhibition of p53's transcriptional function or of the Notch signaling pathway will augment apoptosis induction by cytotoxic agents. Therapeutic strategies based on the novel model, which we review here for the first time, may significantly augment the antitumor actions of cytotoxic agents in CLL and in other malignancies.

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“…[1][2][3][4][5] Survival rates at 5 years for children and adolescents with T-ALL are 70-75%, whereas for adults the rates are 35-40%. 6,7 Therefore, there is a need for novel and less toxic treatment strategies targeting aberrantly activated signaling pathways that increase proliferation, survival and drug resistance of T-ALL cells.…”

Section: Introductionmentioning

confidence: 99%