We used polymerase chain reaction (PCR), differential oligonucleotide hybridization and direct DNA sequencing to retrospectively analyze the N-ras gene of blast cells from the same patient (a) at time of diagnosis of MDS, (b) after the patient had developed AML.
The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%.
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.
Mutations at codon 12, 13, and 61 of the HRAS, KRAS, and NRAS genes were evaluated in 99 cases of pediatric acute myeloid leukemia (AML) using oligonucleotide hybridization to polymerase chain reacted derived products.
Other abnormalities are also relatively specific but occur in only some cases such as NRAS in acute myelogenous leukemia or BCL2 in B-cell acute lymphoblastic leukemia.
The presence of mutations activating the N-ras gene was investigated by the polymerase chain reaction technique in twenty patients with acute myeloblastic leukemia (AML) at onset and in four patients with Ph1 positive chronic myelogeneous leukemia (CML) either in chronic phase or in blast crisis.
HRAS1 and INS genes are relocated but not structurally altered as a result of the t(7;11)(p15;p15) in a clone from a patient with acute myeloid leukaemia (M4).
DNA transfection analyses (tumorigenicity assay) and hybridization to mutation-specific oligonucleotide probes established NRAS mutations in codon 12 or 61 of 4/9 acute myelocytic leukemias (AML) and three AML lines.
DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene.
An activated c-N-ras gene from a 45-year-old patient with AML was isolated by transfection analysis and subjected to molecular cloning and sequence analysis.
Here we demonstrate the presence of a transforming N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia at the outbreak of the acute disease phase.
The data suggest that in addition to coding region mutations in the N-ras gene, mutations in the promoter region that could alter regulation of N-ras expression provide an alternative mechanism of involvement of N-ras in AML.
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.