Format

Send to

Choose Destination
See comment in PubMed Commons below
Blood Rev. 2011 Mar;25(2):83-90. doi: 10.1016/j.blre.2010.09.004. Epub 2010 Oct 20.

Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia.

Author information

1
Institute for Cancer Genetics, Columbia University, NY, USA.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor resulting from the malignant transformation of immature T-cell progenitors. Originally associated with a dismal prognosis, the outcome of T-ALL patients has improved remarkably over the last two decades as a result of the introduction of intensified chemotherapy protocols. However, these treatments are associated with significant acute and long-term toxicities, and the treatment of patients presenting with primary resistant disease or those relapsing after a transient response remains challenging. T-ALL is a genetically heterogeneous disease in which numerous chromosomal and genetic alterations cooperate to promote the aberrant proliferation and survival of leukemic lymphoblasts. However, the identification of activating mutations in the NOTCH1 gene in over 50% of T-ALL cases has come to define aberrant NOTCH signaling as a central player in this disease. Therefore, the NOTCH pathway represents an important potential therapeutic target. In this review, we will update our current understanding of the molecular basis of T-ALL, with a particular focus on the role of the NOTCH1 oncogene and the development of anti-NOTCH1 targeted therapies for the treatment of this disease.

PMID:
20965628
PMCID:
PMC3033461
DOI:
10.1016/j.blre.2010.09.004
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center