C-KIT and FLT3 is a type III receptor tyrosine kinase (RTK) and the c-KIT gene mutation is associated with adult acute myeloid leukemia (AML) patients with t(8;21) or inv(16). The incidence of c-KIT mutation and prognostic significance in pediatric t(8;21)-AML remains uncertain. There were 46 patients (29.1%) with t(8;21)-AML confirmed by cytogenetics and/or RT-PCR (AML1-MTG8 chimeric mRNA) in 158 AML patients treated on Japan pediatric AML cooperative treatment protocol, AML 99. We performed the mutational analyses in TK2 domain (exon 17) of c-KIT, internal tandem duplication (ITD) of FLT3 and TK2 domain (exon 21) of FLT3 using RT-PCR followed by direct sequencing. Eight of 46 patients (17.4%) showed TK2 domain mutation of c-KIT (N822K 3 patients,N822T,D816H,D816V,V825A,A814S 1 patient each). Among them, 5 patients showed 1st relapse within 14 months after diagnosis and received allogenic stem cell transplantation (allo-SCT) in 2nd CR. One of five patients died of 2nd relapse. Two patients who received allo-SCT in 1st CR (at 6 and 8 months after diagnosis) have not relapsed. Two of 38 (5.3%) patients without c-KIT mutation have relapsed. In total, 7 of 46 patients (15.2%) have relapsed in this study. The significant difference between patients with or without c-KIT mutation was observed in 3-year event free survival and relapse rate (p<0.001). FLT3/ITD was found in two patients, and one of them died during chemotherapy. FLT3/TK2 domain mutation was found in only one patient, however this patient has not relapsed. In total, 11 of 46 (23.9%) patients showed RTK mutations in this study. C-KIT mutation was found to be a prognostic factor in pediatric t(8;21)-AML. Although the t(8;21)-AML is classified into a favorable group of AML, t(8;21)-AML with c-KIT mutation should be treated more intensively.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]