MF patients with N/KRAS mutations had shorter 3-year overall survival (OS) (34% vs 58%, p < 0.001) and higher incidence of acute myeloid leukemia at 3 years (18% vs 11%, p = 0.03).
Targeting of the RAS pathway has long been a critical therapeutic challenge in oncology.Burgess et al. examine how the relative expression of mutant and wild-type KRAS modulates clonal fitness and sensitivity to MEK inhibitors in a model of Kras<sup>G12D</sup> mutant acute myeloid leukemia and propose its use as a predictive biomarker.
Somatic mutations that lead to constitutive activation of NRAS and KRAS proto-oncogenes are among the most common in human cancer and frequently occur in acute myeloid leukemia (AML).
Ectopic expression of KRAS, NRAS and MAPK1 attenuated the anti-leukemic activity of miR-181a mimics, thereby validating the relevance of the deregulated miR-181a-RAS network in AML.
Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d).
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.
We investigated mutations of N-RAS and K-RAS by using polymerase chain reaction (PCR)-oligonucleotide hybridization techniques in 40 cases of Chinese leukaemia patients and 17 presently healthy members of a family with high incidence of acute myeloid leukaemia.
By combining allele-specific PCR amplification and a PCR-based quantitation approach, a method has been developed to estimate the mutated K-ras gene content in the blood of AML patients as a percentage of total K-ras.
We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS.
Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis.
We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene.
We examined a prospective cohort of 43 acute myeloid leukemia (AML) patients admitted to the University of Maryland Cancer Center for first and second exon mutations of NRAS and KRAS using PCR and DNA sequence analysis.