KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group.
Patients with t(8;21) acute myeloid leukemia (AML) are considered to have a good prognosis; however, approximately 50% of them relapse. The genetic alterations associated with a poor outcome in t(8;21) AML remain unknown. Recently, aberrations of receptor tyrosine kinases (RTKs) were frequently found in patients with AML. However, the prevalence and prognostic impact of RTK aberrations in pediatric t(8;21) AML remains undetermined. Here, we found the kinase domain mutations of the KIT gene in 8 (17.4%) of 46 patients with t(8;21) AML among newly diagnosed pediatric patients with AML treated on the AML99 protocol in Japan. Significant differences between patients with or without KIT mutations were observed in the 4-year overall survival (50.0% versus 97.4%, P = .001), disease-free survival (37.5% versus 94.7%, P < .001) and relapse rate (47.0% versus 2.7%, P < .001). Furthermore, FLT3 internal tandem duplication was found in only 2 (4.3%) patients. These results suggested that KIT mutations are strongly associated with a poor prognosis in pediatric t(8;21) AML.
Shimada
Akira
A
Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Kitatachibana, Gunma 377-8577, Japan.
Taki
Tomohiko
T
Tabuchi
Ken
K
Tawa
Akio
A
Horibe
Keizo
K
Tsuchida
Masahiro
M
Hanada
Ryoji
R
Tsukimoto
Ichiro
I
Hayashi
Yasuhide
Y
D000293:Adolescent; D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D015995:Prevalence; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3