Alteration of NOTCH1 in T-cell Acute Lymphoblastic Leukemia and Development of Target Therapeutic Agent / 임상소아혈액종양
Clinical Pediatric Hematology-Oncology
;
: 1-8, 2014.
Article
in Korean
| WPRIM
| ID: wpr-788509
ABSTRACT
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 therapeutic 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 gamma-secretase inhibitor, blocking a proteolytic step required for creation 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oncogenes
/
Transcription Factors
/
T-Lymphocytes
/
Gene Expression
/
Incidence
/
Genes, T-Cell Receptor
/
Amyloid Precursor Protein Secretases
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Type of study:
Incidence study
/
Prognostic study
Limits:
Child
/
Humans
Language:
Korean
Journal:
Clinical Pediatric Hematology-Oncology
Year:
2014
Type:
Article
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