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KMID : 0387820140210010001
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Clinical Pediatric Hematology-Oncology
2014 Volume.21 No. 1 p.1 ~ p.8
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Alteration of NOTCH1 in T-cell Acute Lymphoblastic Leukemia and Development of Target Therapeutic Agent
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Rho Jung-Hee
Jeon In-Sang
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Abstract
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T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 10-15% of entire ALL in children. The outcome of T-ALL has been improved through the intensified ther-apeutic strategy, however, it is still a more aggressive disease. In T-ALL a couple of transcription factor oncogenes are known to be relocated to the juxtaposition of T-cell receptor genes, potent promoter, by chromosome translocation. However the incidence of each chimeric gene formation in T-ALL is less than 5% and their clinical significance as a prognostic marker is lacking. A decade ago it was identified that activating mutations in NOTCH1 in about 60% of T-ALL. After then, activating NOTCH1 mutations present in T-ALL have been extensively investigated with regard to understanding its molecular pathogenesis, its prognostic significance, and developing molecularly tailored novel agents. Small molecule ?-secretase inhibitor, blocking a proteolytic step required for crea-tion of a fragment of NOTCH intracellular domain which actually act as a controller of its target gene expression, was tried as a target therapeutic drug for T-ALL. Although outcome of this drug was not satisfactory, challenges have been launched to develop new drugs which specifically act on the aberrant behavior of mutated NOTCH1 in T-ALL.
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KEYWORD
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T-ALL, NOTCH1, Gamma-secretase inhibitor
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