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K-ras mutations and N-ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements
Article first published online: 10 JAN 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 4, pages 950–956, 15 February 2006
How to Cite
Liang, D.-C., Shih, L.-Y., Fu, J.-F., Li, H.-Y., Wang, H.-I., Hung, I.-J., Yang, C.-P., Jaing, T.-H., Chen, S.-H. and Liu, H.-C. (2006), K-ras mutations and N-ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. Cancer, 106: 950–956. doi: 10.1002/cncr.21687
- Issue published online: 3 FEB 2006
- Article first published online: 10 JAN 2006
- Manuscript Accepted: 29 SEP 2005
- Manuscript Revised: 26 SEP 2005
- Manuscript Received: 16 AUG 2005
- National Science Council, Taiwan. Grant Number: NSC93-2314-B-195-008
- Mackay Memorial Hospital, Taipei, Taiwan. Grant Number: MMH-E-94009
- National Health Research Institute, Taiwan. Grant Number: NHRI-EX94-9434SI
- N-Ras mutations;
- K-Ras mutations;
- childhood acute lymphoblastic leukemia;
- childhood acute myeloid leukemia;
- MLL rearrangements
It is believed that Ras mutations drive the proliferation of leukemic cells. The objective of this study was to investigate the association of Ras mutations with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) with special reference to the presence or absence of mixed-lineage leukemia gene (MLL) rearrangements.
Bone marrow samples from 313 children with B-precursor ALL and 130 children with de novo AML were studied at diagnosis. Southern blot analysis was used to detect MLL rearrangements, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was used to detect common MLL fusion transcripts. Complementary DNA panhandle PCR was used to identify the infrequent or unknown MLL partner genes. DNA PCR or RT-PCR followed by direct sequencing was performed to detect mutations at codons 12, 13, and 61 of the N-Ras and K-Ras genes.
Twenty of 313 patients with B-precursor ALL and 17 of 130 patients with de novo AML had MLL rearrangements. N-Ras mutations were detected in 2 of 20 patients with MLL-positive ALL and in 27 of 293 patients with MLL-negative ALL (P = 1.000). N-Ras mutations were detected in 2 of 17 patients with MLL-positive AML and in 14 of 113 patients with MLL-negative AML (P = 1.000). K-Ras mutations were present in 8 of 20 patients with MLL-positive ALL compared with 32 of 293 patients with MLL-negative ALL (P = 0.001). K-Ras mutations were detected in 3 of 17 patients with MLL-positive AML compared with 5 of 113 patients with MLL-negative AML (P = 0.069).
Ras mutations were detected in 20.8% of patients with childhood B-precursor ALL and in 17.7% of patients with childhood AML. MLL-positive B-precursor ALL was associated closely with Ras mutations (50%), especially with K-Ras mutations (40%), whereas MLL-positive AML was not associated with Ras mutations. Cancer 2006. © 2006 American Cancer Society.