Nucleophosmin (NPM1-A) and FMS-like tyrosine kinase 3 (FLT3/ITD) mutations in acute myeloid leukaemia with a normal karyotype: frequency and prognostic significance

Background:Treatment of acute myeloid leukaemia (AML) with a normal karyotype (NK) has always been a challenge for clinicians. This is because it affects the majority of AML patients and falls into the intermediate-risk group that needs further risk stratifications.Aim of the study: The current study aimed to verify the importance and significance of analysis of NPM1-A and FLT3/ITD mutations, alone and combined, and their relation to prognostic criteria.Patients and methods: Thirty-five patients with de-novo AML with a median age of 33 years (19–60) and ten healthy volunteers (the control group) were included. All participants were subjected to clinical examination, routine laboratory investigations and (for patients only) bone marrow examination and cytogenetic analysis by the G-banding technique. Using the genomic PCR (RT and conventional) technique, NPM1 type A and FLT3/ITD mutations were studied in the NK-AML patients and controls. Their impacts were evaluated alone and combined.Results: After cytogenetic analysis 20/35 (57.1) patients proved to be of NK; their median age was 37.5 (19–60) years. This NK-AML group and control group were examined for NPM1 and FLT3/ITD mutations. None of the controls had either mutation. The NK group was categorized into NPM1+ or NPM1− and FLT3+ or FLT3−. Their frequencies were 40% (8), 60% (12) and 40% (8), 60 (12), respectively. These subgroups were assessed after induction chemotherapy for achievement of complete remission (CR), which was recorded in 62.5% of NPM1-positive patients and 0% of NPM1-negative patients, showing a significant difference with a P value of 0.004, whereas nonsignificant difference between FLT3-positive and FLT3-negative patients was recorded. The NK patients were further subdivided into four genetic subgroups: NPM+/FLT3−, NPM−/FLT3−, NPM+/FLT3+ and NPM−/FLT3+, with frequencies of 15, 45, 25 and 15%, respectively. Sixty per cent of patients who achieved CR were NPM1+/FLT3−. Furthermore, 100% of this subgroup achieved CR, 40% of NPM+/FLT3+ also achieved CR, but none of the NPM−/FLT3− and NPM1−/FLT3+ patients did.Conclusion: Genotypes defined by the mutational status of NPM1, FLT3 are associated with the outcome of treatment in NK-AML patients.