Prognostic implication of N-RAS gene mutations in Egyptian adult acute myeloid leukemia.
The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). The aim of the present work is to study the frequency and prognostic significance of N-RAS gene mutations (N-RASmut) in de novo Egyptian adult AML. Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for N-RAS mutations. In 12.7% (19/150) AML cases, N-RAS gene mutations were found and were observed more frequently in the FAB subtype M4eo (P = 0.028) and with codon 12, 13 (14 of 19; 73.7%). Patients with N-RAS mutation had a significant lower peripheral and marrow blasts (P = 0.004, P = 0.03) and clinical outcome did not improve more than in patients without mutation. In patients with N-RAS gene mutation vs. those without, complete remission rate was (63.2% vs. 56.5%; P = 0.46), resistant disease (15.8% vs. 23.6%; P = 0.51), three years overall survival (44% vs 42%; P= 0.85) and disease free survival (42.1% vs. 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = 0.002), followed by cytogenetics (P = 0.004). FAB types, N-RAS mutation and leukocytosis were the least important. In conclusion, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML.
Elghannam
Doaa M
DM
Department of Clinical Pathology, Hematology Unit, Faculty of Medicine, Mansoura University, USA.
Abousamra
Nashwa Khayrat
NK
Shahin
Doaa A
DA
Goda
Enas F
EF
Azzam
Hanan
H
Azmy
Emad
E
El-Din
Manal Salah
MS
El-Refaei
Mohamed F
MF
D000328:Adult; D001752:Blast Crisis / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D001853:Bone Marrow / Q000473:pathology; D018572:Disease-Free Survival; D004534:Egypt / Q000453:epidemiology; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015996:Survival Rate