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Acute Leukemias

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

Leukemia volume 22, pages 303–307 (2008)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by grants MMH-E-94009 and MMH-E-95009 from the Mackay Memorial Hospital, grant NSC 94-2314-B-195-003 from the National Science Council and grant NHRI-EX96-9434SI from the National Health Research Institute, Taiwan.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan

    L-Y Shih & C-F Huang

  2. School of Medicine, Chang Gung University, Taoyuan, Taiwan

    L-Y Shih, C-L Lai & T-H Lin

  3. Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan

    D-C Liang, Y-T Chang, H-C Liu, L-Y Wang & T-C Yeh

  4. Chang Gung Children's Hospital, Linkou, Taiwan

    C-P Yang, I-J Hung & T-H Jaing

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  1. L-Y Shih
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Correspondence to D-C Liang.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Shih, LY., Liang, DC., Huang, CF. et al. 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. Leukemia 22, 303–307 (2008). https://doi.org/10.1038/sj.leu.2404995

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