Abnormalities of Receptor Tyrosine Kinases in Childhood Leukemia

概要

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Point mutations of D835/I836 in the activation loop of the second tyrosine kinase (TK) domain of the FLT3 gene have been reported in adult acute myeloid leukemia (AML), but not in pediatric AML or acute lymphoblastic leukemia (ALL). To determine the frequency and clinical significance of mutations of the FLT3 TK, c-KIT, and PDGFRA genes in pediatric leukemias, we examined 17 cell lines and 150 fresh pediatric leukemias of AML, and 47 cell lines and 167 fresh pediatric leukemias of ALL. We found the mutations in 6 (4.7%) of 127 pediatric ALL patients more than one year old, and 8 (20%) of 40 infant ALL patients. All the mutations were heterozygous mutations. Remarkably, FLT3 TK-mutations were frequently found in 4 (21.5%) of 19 hyperdiploid ALL patients. The infant ALL patients with mutations tended to have a poorer prognosis than those without the mutations, while pediatric ALL patients more than one year with mutations had a good prognosis. We also found TK-mutations in 2 of 11 leukemic cell lines with MLL rearrangements. c-KIT mutations were found in only one patient with t (8;21) out of 150 AML patients. Mutations of PDGFRA gene were found in 2 patients of 150 AML patients. These results suggested that mutations of the FLT3, c-KIT and PDGFRA genes may be one of the second hit mutations involved in the development of pediatric ALL and AML.
特定非営利活動法人　日本小児血液・がん学会の論文