Leukemia is an uncontrolled growth of blood cells. This uncontrolled cell division
occurs due to the mutation occurring in proto-oncogenes such as NRAS, c-kit, FLT3,
NPM1, KRAS etc in either myeloid or lymphocytic lineages. When the NRAS is in
active state it stimulate a cascade of intracellular pathway leading to normal cell
division and proliferation. However, the mutations in NRAS gene causes a prolonged
or sustained activation of NRAS leading to uncontrolled proliferation and
differentiation of cells resulting in acute myeloid leukemia (AML). The study is
conducted to determine the frequency of NRAS mutation and its prognostic
significance in Pakistani AML patients. Peripheral blood samples were taken from 31
de novo AML ptients. Most of the patients in AML cohort were male (68%). In the
present investigation, NRAS malformations in exon2 were analyzed for a cohort of 31
AML patients and correlated the results to teir cytogenetics, clinical and hematological
parameters. The cohort under study was divided into two categories of age group:
pediatric group (13%) and Adult group (87%). Two patients were observed to exhibit
similar NRAS mutation in codon 63 and 68 which is reported for the first time in present
study. Both the patients (6.45%) were adults showing insertion of one nucleotide
basepair adenine (A) at position 319 (codon 63) causing frameshift in the subsequent
amino acid sequence. One of them was observed to have another single basepair
insertion of thymine (T) at position 336 while the other was detected to have a two
basepair insertion of adenine and thymine (TA) at position 336 (codon 68) and 337
(codon 69) leading to the formation of a premature stop codon ending the amino acid
translation. AML patients, INM5 and INM7 who manifested NRAS mutations were
observed to have hemoglobin (Hb) level 5.4 or 8.5g/dL respectively. One mutant
individual (INM5) was a female (cytogenetically abnormal) and was pregnant at the
time of diagnosis. She was observed to have platelet count; 6.77× 109/L, total leucocyte
count; 11× 109/L however the blast cells percentage was 13% (the general value to
diagnosed AML is 20%). The male was observed to have platelet count; 11× 109/L,
total leucocyte count; 4 × 109/L while the blast cell count was 26%. The mutant and
non-mutant patients when compared in terms of hematological and clinical parameters
a noteworthy correlation was found between blast cell percentage, white blood cell
count, cytogenetic status which are the major parameters to detect AML.