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K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements.
Cancer. 2006 Feb 15; 106(4):950-6.C

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

Authors+Show Affiliations

Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16404744

Citation

Liang, Der-Cherng, et al. "K-Ras Mutations and N-Ras Mutations in Childhood Acute Leukemias With or Without Mixed-lineage Leukemia Gene Rearrangements." Cancer, vol. 106, no. 4, 2006, pp. 950-6.
Liang DC, Shih LY, Fu JF, et al. K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. Cancer. 2006;106(4):950-6.
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., & 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(4), 950-6.
Liang DC, et al. K-Ras Mutations and N-Ras Mutations in Childhood Acute Leukemias With or Without Mixed-lineage Leukemia Gene Rearrangements. Cancer. 2006 Feb 15;106(4):950-6. PubMed PMID: 16404744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. AU - Liang,Der-Cherng, AU - Shih,Lee-Yung, AU - Fu,Jen-Fen, AU - Li,Huei-Ying, AU - Wang,Hsiu-I, AU - Hung,Iou-Jih, AU - Yang,Chao-Ping, AU - Jaing,Tang-Her, AU - Chen,Shu-Huey, AU - Liu,Hsi-Che, PY - 2006/1/13/pubmed PY - 2006/3/29/medline PY - 2006/1/13/entrez SP - 950 EP - 6 JF - Cancer JO - Cancer VL - 106 IS - 4 N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/16404744/K_Ras_mutations_and_N_Ras_mutations_in_childhood_acute_leukemias_with_or_without_mixed_lineage_leukemia_gene_rearrangements_ L2 - https://doi.org/10.1002/cncr.21687 DB - PRIME DP - Unbound Medicine ER -