RAS mutations in pediatric leukemias with MLL gene rearrangements

Nidal Mahgoub, Robert I. Parker, Matthew R. Hosler, Pamelyn Close, Naomi J. Winick, Margaret Masterson, Kevin M. Shannon, Carolyn A. Felix

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, I was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.

Original languageEnglish (US)
Pages (from-to)270-275
Number of pages6
JournalGenes Chromosomes and Cancer
Volume21
Issue number3
DOIs
StatePublished - Mar 1998

Fingerprint

Gene Rearrangement
Leukemia
Pediatrics
Acute Myeloid Leukemia
Mutation
Mutation Rate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genes
Topoisomerase II Inhibitors
Enzyme Assays
Cytogenetics
Chromosomes
Alleles
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

RAS mutations in pediatric leukemias with MLL gene rearrangements. / Mahgoub, Nidal; Parker, Robert I.; Hosler, Matthew R.; Close, Pamelyn; Winick, Naomi J.; Masterson, Margaret; Shannon, Kevin M.; Felix, Carolyn A.

In: Genes Chromosomes and Cancer, Vol. 21, No. 3, 03.1998, p. 270-275.

Research output: Contribution to journalArticle

Mahgoub, N, Parker, RI, Hosler, MR, Close, P, Winick, NJ, Masterson, M, Shannon, KM & Felix, CA 1998, 'RAS mutations in pediatric leukemias with MLL gene rearrangements', Genes Chromosomes and Cancer, vol. 21, no. 3, pp. 270-275. https://doi.org/10.1002/(SICI)1098-2264(199803)21:3<270::AID-GCC14>3.0.CO;2-T
Mahgoub, Nidal ; Parker, Robert I. ; Hosler, Matthew R. ; Close, Pamelyn ; Winick, Naomi J. ; Masterson, Margaret ; Shannon, Kevin M. ; Felix, Carolyn A. / RAS mutations in pediatric leukemias with MLL gene rearrangements. In: Genes Chromosomes and Cancer. 1998 ; Vol. 21, No. 3. pp. 270-275.
@article{f66b993f5d7843e3b86987c430b0b116,
title = "RAS mutations in pediatric leukemias with MLL gene rearrangements",
abstract = "Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, I was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.",
author = "Nidal Mahgoub and Parker, {Robert I.} and Hosler, {Matthew R.} and Pamelyn Close and Winick, {Naomi J.} and Margaret Masterson and Shannon, {Kevin M.} and Felix, {Carolyn A.}",
year = "1998",
month = "3",
doi = "10.1002/(SICI)1098-2264(199803)21:3<270::AID-GCC14>3.0.CO;2-T",
language = "English (US)",
volume = "21",
pages = "270--275",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - RAS mutations in pediatric leukemias with MLL gene rearrangements

AU - Mahgoub, Nidal

AU - Parker, Robert I.

AU - Hosler, Matthew R.

AU - Close, Pamelyn

AU - Winick, Naomi J.

AU - Masterson, Margaret

AU - Shannon, Kevin M.

AU - Felix, Carolyn A.

PY - 1998/3

Y1 - 1998/3

N2 - Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, I was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.

AB - Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, I was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.

UR - http://www.scopus.com/inward/record.url?scp=0031881426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031881426&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2264(199803)21:3<270::AID-GCC14>3.0.CO;2-T

DO - 10.1002/(SICI)1098-2264(199803)21:3<270::AID-GCC14>3.0.CO;2-T

M3 - Article

VL - 21

SP - 270

EP - 275

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 3

ER -