K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements

Der Cherng Liang, Lee Yung Shih, Jen F. Fu, Huei Ying Li, Hsiu I. Wang, Iou J. Hung, Chao Ping Yang, Tang H. Jaing, Shu Huey Chen, Hsi C. Liu

Research output: Contribution to journalArticle

73 Citations (Scopus)

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 Mil-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.

Original languageEnglish
Pages (from-to)950-956
Number of pages7
JournalCancer
Volume106
Issue number4
DOIs
Publication statusPublished - Feb 15 2006
Externally publishedYes

Fingerprint

Gene Rearrangement
Leukemia
Acute Myeloid Leukemia
Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genes
Reverse Transcriptase Polymerase Chain Reaction
Polymerase Chain Reaction
ras Genes
Gene Fusion
Southern Blotting
Codon

Keywords

  • Childhood acute lymphoulastic leukemia
  • Childhood acute myeloid leukemia
  • K-Ras mutations
  • MLL rearrangements
  • N-Ras mutations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liang, D. C., Shih, L. Y., Fu, J. F., Li, H. Y., Wang, H. I., Hung, I. J., ... 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), 950-956. https://doi.org/10.1002/cncr.21687

K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. / Liang, Der Cherng; Shih, Lee Yung; Fu, Jen F.; Li, Huei Ying; Wang, Hsiu I.; Hung, Iou J.; Yang, Chao Ping; Jaing, Tang H.; Chen, Shu Huey; Liu, Hsi C.

In: Cancer, Vol. 106, No. 4, 15.02.2006, p. 950-956.

Research output: Contribution to journalArticle

Liang, DC, Shih, LY, Fu, JF, Li, HY, Wang, HI, Hung, IJ, Yang, CP, Jaing, TH, Chen, SH & Liu, HC 2006, 'K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements', Cancer, vol. 106, no. 4, pp. 950-956. https://doi.org/10.1002/cncr.21687
Liang, Der Cherng ; Shih, Lee Yung ; Fu, Jen F. ; Li, Huei Ying ; Wang, Hsiu I. ; Hung, Iou J. ; Yang, Chao Ping ; Jaing, Tang H. ; Chen, Shu Huey ; Liu, Hsi C. / K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements. In: Cancer. 2006 ; Vol. 106, No. 4. pp. 950-956.
@article{918d1abf72364789b2bd5072daf88f77,
title = "K-Ras mutations and N-Ras mutations in childhood acute leukemias with or without mixed-lineage leukemia gene rearrangements",
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 Mil-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.",
keywords = "Childhood acute lymphoulastic leukemia, Childhood acute myeloid leukemia, K-Ras mutations, MLL rearrangements, N-Ras mutations",
author = "Liang, {Der Cherng} and Shih, {Lee Yung} and Fu, {Jen F.} and Li, {Huei Ying} and Wang, {Hsiu I.} and Hung, {Iou J.} and Yang, {Chao Ping} and Jaing, {Tang H.} and Chen, {Shu Huey} and Liu, {Hsi C.}",
year = "2006",
month = "2",
day = "15",
doi = "10.1002/cncr.21687",
language = "English",
volume = "106",
pages = "950--956",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

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 F.

AU - Li, Huei Ying

AU - Wang, Hsiu I.

AU - Hung, Iou J.

AU - Yang, Chao Ping

AU - Jaing, Tang H.

AU - Chen, Shu Huey

AU - Liu, Hsi C.

PY - 2006/2/15

Y1 - 2006/2/15

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 Mil-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.

AB - 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 Mil-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.

KW - Childhood acute lymphoulastic leukemia

KW - Childhood acute myeloid leukemia

KW - K-Ras mutations

KW - MLL rearrangements

KW - N-Ras mutations

UR - http://www.scopus.com/inward/record.url?scp=32544448534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32544448534&partnerID=8YFLogxK

U2 - 10.1002/cncr.21687

DO - 10.1002/cncr.21687

M3 - Article

C2 - 16404744

AN - SCOPUS:32544448534

VL - 106

SP - 950

EP - 956

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 4

ER -