Neuroblastoma Rat Sarcoma viral oncogene homolog (NRAS), a membrane-bound protein with
GTPase activity that functions as an important regulatory element in the signal transduction
pathways, is an essential constituent of fundamental cellular processes such as cell polarity,
proliferation, differentiation, adhesion, migration, and apoptosis. Mutations in the NRAS gene
are frequent genetic aberrations, reported in approximately 11%-30% of AML patients. The aim
of this study was to detect the mutations in NRAS exon 1 of AML patients of Pakistan, to
identify the correlation between the mutation and various clinical and hematological parameters
and to determine the prognostic relevance of NRAS mutations. For the purpose of this study
DNA was isolated from the blood samples of AML patients (n=31) and were sequenced for exon
1 of NRAS gene. A unique missense mutation, NRAS-I36R (239T>G) sustituting Isoleucine
with Arginine residue in the Switch II motif of NRAS exon 1, was observed in an adult female
AML patient (3.2%). Using Chi square test, the association of mutation with several parameters
was assessed. All the parameters were found to be statistically not associated with the occurrence
of mutation. Age, gender, hepatomegaly and splenomegaly were observed to be non-significantly
associated with NRAS mutation, as is reported by earlier investigations. The mutant patient
belonged to M2 FAB subtype, which is perceived to have high incidence of NRAS mutations.
Furthermore, the results illustrate that the patient exhibited low levels of TLC, platelets,
Hemoglobin level and RBC count and increased level of blast cell %, yet no significant
association with mutation. These finding corroborated with previous studies on NRAS
mutations. Over the four month follow up on the progress of the mutant patient, it was clear that
the patient was demonstrating poor response to treatment with rapidly decreasing levels of
hemoglobin, TLC, RBC count, platelet count and increasing blast cell percentage. Thus, NRASI36R bearing patient may have an unfavorable outcome. However, due to small frequency of
mutations in present cohort, a significant answer cannot be retrieved, thus analysis of large
number of patients is required to confirm these findings. Further studies on NRAS related
mutations are needed to explain their oncogenic effect on GTPase hydrolysis, resulting
tumorigenesis and their prognostication in AML and other neoplasms.