T-¼¼Æ÷Çü ±Þ¼º¸²ÇÁ±¸¼º¹éÇ÷º´¿¡¼ NOTCH1ÀÇ º¯Çü°ú Ç¥ÀûÄ¡·áÁ¦ °³¹ß
Alteration of NOTCH1 in T-cell Acute Lymphoblastic Leukemia and Development of Target Therapeutic Agent
Clinical Pediatric Hematology-Oncology 2014³â 21±Ç 1È£ p.1 ~ p.8
³ëÁ¤Èñ(Rho Jung-Hee) - °¡Ãµ´ëÇб³ ÀÇÇÐÀü¹®´ëÇпø ¼Ò¾Æ°úÇб³½Ç
ÀüÀλó(Jeon In-Sang) - °¡Ãµ´ëÇб³ ÀÇÇÐÀü¹®´ëÇпø ¼Ò¾Æ°úÇб³½Ç
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 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.
Å°¿öµå
T-ALL, NOTCH1, Gamma-secretase inhibitor
KMID :
0387820140210010001
¿ø¹® ¹× ¸µÅ©¾Æ¿ô Á¤º¸
µîÀçÀú³Î Á¤º¸
À¯È¿¼º°á°ú(Recomendation)