Mutations of the RAS family in patients with acute myeloid leukaemia
Authors:
A. Ďuriníková 1,2; A. Folta 2; M. Čulen 1,2,3; Z. Herudková 1,2; D. Al Tukmachi 3; J. Mayer 1,2,3; I. Ježíšková 1,2
Authors‘ workplace:
Lékařská fakulta, Masarykova univerzita, Brno
1; Interní hematologická a onkologická klinika, Fakultní nemocnice Brno, Brno
2; CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno
3
Published in:
Transfuze Hematol. dnes,25, 2019, No. 4, p. 331-338.
Category:
Review/Educational Papers
Overview
Somatic mutations in RAS (rat sarcoma viral oncogene homolog) proto-oncogenes lead to constitutive activation of RAS signalling pathways impacting cellular proliferation, differentiation and apoptosis. RAS mutations are detected in approximately one fifth of patients with acute myeloid leukaemia (AML). Typically, the aberrations are missense heterozygous point mutations localized in codons G12, G13 and Q61 in exons 2 and 3, respectively. In AML, NRAS is the most frequently mutated gene of the RAS family. Simultaneously mutated NRAS and KRAS genes in one patient are possible, but rare. In approximately 10% of AML patients, multiple NRAS mutations are detected. The RAS mutations occur with higher frequency in AML patients with chromosomal aberrations inv(16)/t(16;16), t(8;21), inv(3)/t(3;3). In patients with normal karyotype, the RAS genes are frequently co-mutated with the NPM1 and DNMT3A genes. Most of the large cohort studies did not demonstrate any implication of RAS mutations on overall survival, and its occurrence was not significantly associated with any clinical parameters. During leukaemogenesis, RAS mutations play a role as late secondary events supporting increased proliferation of AML subclones.
The aim of this work is to summarize the current knowledge about the RAS gene family and its significance in patients with AML.
Keywords:
acute myeloid leukaemia – AML – RAS – mutations
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