Cooperating mutations of receptor tyrosine kinases and Ras genes in childhood core-binding factor acute myeloid leukemia and a comparative analysis on paired diagnosis and relapse samples

• Published in: Leukemia Vol. 22; no. 2; pp. 303 - 307
• Main Authors: Shih, L-Y, Liang, D-C, Huang, C-F, Chang, Y-T, Lai, C-L, Lin, T-H, Yang, C-P, Hung, I-J, Liu, H-C, Jaing, T-H, Wang, L-Y, Yeh, T-C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2008; Nature Publishing; Nature Publishing Group
• Subjects: Acute myeloid leukemia; Adolescent; Binding; Biological and medical sciences; Bone Marrow - pathology; c-Kit protein; Cancer Research; Cell receptors; Child; Child, Preschool; Children; Comparative analysis; Core Binding Factors; Critical Care Medicine; Diagnosis; DNA Mutational Analysis; Exons; Gene mutations; Genes, ras - genetics; Genetic aspects; Health aspects; Hematologic and hematopoietic diseases; Hematology; Humans; Intensive; Internal Medicine; K-Ras protein; Kinases; Leukemia; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemogenesis; Medical diagnosis; Medical sciences; Medicine; Medicine & Public Health; Mutation; Oncology; original-article; Pathogenesis; Proto-Oncogene Proteins c-kit - genetics; Ras genes; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptors; Recurrence; Time Factors; Tyrosine; Taiwan; mutation; receptor tyrosine kinase; core-binding factor; childhood acute myeloid leukemia; Human; Acute myelogenous leukemia; Relapse; Hematology; Transcription factor CBF; Receptor tyrosine kinase; Malignant hemopathy; c-KIT mutation; C-Onc gene; Ras mutation; Genetics; Diagnosis; Mutation; Ras gene; Child; kit Gene; Comparative study; Protooncogene; CSF1R mutation; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2404995

c-KIT mutations have been described in core-binding factor (CBF) acute myeloid leukemia (AML) at diagnosis. The role of c-KIT mutations in the relapse of CBF–AML is not clear. The role of CSF1R mutation in the pathogenesis of AML remains to be determined. We analyzed receptor tyrosine kinases (RTKs) and Ras mutations on 154 children with AML. Also, we examined the paired diagnosis and relapse samples in CBF–AML. CBF–AML accounted for 27% (41/154). c-KIT mutations were detected in 41.5% of CBF–AML at diagnosis (6 in exon 8, 10 in exon 17 and 1 in both exons 8 and 17) , FLT3– TKD 2.7%, N- Ras mutations 7.3% and K- Ras mutations 4.9%. FLT3– LM and CSF1R mutations were not found in CBF–AML. The mutations of RTKs and Ras were mutually exclusive except for one patient who had both c-KIT and N- Ras mutations. Eight of the 41 CBF–AML patients relapsed; four patients retained the identical c-KIT mutation patterns as those at diagnosis, the remaining four without c-KIT mutations at diagnosis did not acquire c-KIT mutations at relapse. Our study showed that 54% of childhood CBF–AML had RTKs and/or Ras mutations; c-KIT but not CSF1R mutations play a role in the leukemogenesis of childhood CBF–AML.