Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized byanomalous proliferation, inhibition of differentiation and expansion of leukemic cells blocked at the early stage of hematopoiesis. The molecular markers have become a smart tool to further division of AML patients into subgroups. Nucleophosmin (NPM1) mutations are found in approximately 30% of adult AML patients and are associated with a favorable outcome when detected in absence of FLT3-ITD mutation. Over 50 molecular NPM1 mutation variants have been identified; the most common one is NPM1-A mutation. The current study aims to detect; the frequency of NPM1-A in Iraqi adult newly diagnosed AML patients using real time -PCR technique and evaluate the relationship of NPM1-A with age, gender, total white blood cell (WBC) count and FAB subtypes of the disease. The frequency of NPM1-A mutation in newly diagnosed AML patients was 18.86%. Age was non-significantly higher in NPM1-A mutated patients than in patients without mutation (P=0.538). The NPM1-A mutation was predominantly seen in male (P= 0.069). The mutation was non-significantly higher among monocytic subtypes (M5+M4) compared with the other subtypes of the disease (P=0.916). In the NPM1 mutated group, the total WBC count was non-significantly higher than the non-mutated group (P=0.302). These findings suggest; Real time-PCR technique using TaqMan probe was very specific molecular test for this mutation. Mutated NPM1-A patients were associated with increased age, a higher total WBC count, male predominance and the monocytic subtypes of the disease.

Evaluation of related flow cytometry parameters with FAB subtype of acute myeloid leukemia associated with histological assessment

“…Many of Iraqi and international studies showed that the more than half of adult patients had hepatomegaly, splenomegaly or lymph nod enlargement at diagnosis that could be appreciated with physical examination also that the degree of organomegaly was more noticeable in children than in adults. Bone pain appeared in the acute myeloid leukemia cases is nearly similar to other Iraqi studies [19,9]. Bone pain is a direct consequence of bone marrow expansion.…”

Characterization of NPM1 and FLT3-ITD Mutations in Iraqi Patients with AML

“…This close to Notopuro et al 21 with blast cells of (79.5%). Patients with NPM1 mutation had significantly higher WBC count mean (49.56±15.77×10*9/L) as compared with AML without any mutation (29.36±16.52×10*9/L) similar to findings of Döhner et al and 22 but different from Abdulateef et al 16 which reported that WBC count was non-significantly higher than in non-mutated group. Despite low mean of RBC count, hemoglobin levels and platelets count in AML patients, there were no significant difference among different groups, low levels of these parameters is a logical consequence with AML which is a cancer of the myeloid linage of blood cells, characterized by the rapid growth of abnormal cells that impede normal blood cell production and this will cause anemia, pallor and bleeding tendency.…”

“…However, Chauhan et al 15 disagree in reporting FLT3-ITD mutation in males more than females. NPM1 mutation was found in (10.34%) of the patients and this was not so far from Abdulateef et al 16 who detected it in (18.86%) of the patients. NPM1 mutation was reported more in males in (16.1%) of them than in females (3.7%), this results are similar to Abdulateef et al 16 with a detection in (28.1%) of males and (4.7%) of females.…”

“…NPM1 mutation was found in (10.34%) of the patients and this was not so far from Abdulateef et al 16 who detected it in (18.86%) of the patients. NPM1 mutation was reported more in males in (16.1%) of them than in females (3.7%), this results are similar to Abdulateef et al 16 with a detection in (28.1%) of males and (4.7%) of females. On the other hand, this differs from Dhahir and Dhahi 17 who reported NPM1 mutation in (60%) of females more than seen in males (37.5%).…”

Detection of FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) Mutations from Marrow Tissues in Patients with Acute Myeloid Leukaemia

“…3,23 As for the NPM1 mutation, our findings are consistent with that of others in which no significant differences were observed between the mean full blood count values and the mutation status. 22,24 Likewise, we did not find any significant association between hyperleukocytosis, severe anaemia, and severe thrombocytopenia, and the mutation. However, Abdullah et (2020) showed that their patients with NPM1 mutation had significantly lower haemoglobin levels.…”