» Articles » PMID: 9523205

RAS Mutations in Pediatric Leukemias with MLL Gene Rearrangements

Overview
Date 1998 Apr 2
PMID 9523205
Citations 10
Authors
Affiliations
Soon will be listed here.
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, 1 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.

Citing Articles

The Impact of PI3-kinase/RAS Pathway Cooperating Mutations in the Evolution of -rearranged Leukemia.

Esposito M Hemasphere. 2019; 3(3):e195.

PMID: 31723831 PMC: 6746018. DOI: 10.1097/HS9.0000000000000195.


Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants.

Driessen E, Van Roon E, Spijkers-Hagelstein J, Schneider P, De Lorenzo P, Valsecchi M Haematologica. 2013; 98(6):937-44.

PMID: 23403319 PMC: 3669451. DOI: 10.3324/haematol.2012.067983.


The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial.

Marks D, Moorman A, Chilton L, Paietta E, Enshaie A, Dewald G Haematologica. 2013; 98(6):945-52.

PMID: 23349309 PMC: 3669452. DOI: 10.3324/haematol.2012.081877.


Secondary mutations in t(4;11) leukemia patients.

Prelle C, Bursen A, Dingermann T, Marschalek R Leukemia. 2012; 27(6):1425-7.

PMID: 23242105 PMC: 3677139. DOI: 10.1038/leu.2012.365.


Temporal dissection of K-ras(G12D) mutant in vitro and in vivo using a regulatable K-ras(G12D) mouse allele.

Wang Z, Feng Y, Bardeesy N, Bardessy N, Wong K, Liu X PLoS One. 2012; 7(5):e37308.

PMID: 22606359 PMC: 3350485. DOI: 10.1371/journal.pone.0037308.