Journal
BLOOD REVIEWS
Volume 25, Issue 2, Pages 83-90Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2010.09.004
Keywords
T-ALL; NOTCH; Gamma-secretase inhibitors; Targeted therapy; Prognosis; Leukemia
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Funding
- Merck
- Pfizer
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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 NOTCH] 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. (C) 2010 Elsevier Ltd. All rights reserved.
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