5th World Congress on Cancer Therapy
Armed Forces Institute of Pathology, Pakistan
Title: The Frequency of nucleophosmin1 gene mutation in newly diagnosed patients of acute myeloid leukaemia
Biography: Muhammad Ayyub
Introduction: Nucleophosmin1 (NPM1) gene mutation is the most frequently occurring gene mutation in Acute Myeloid Leukemia (AML) accounting for 35 to 50% of the AML patients. It encodes the nucleophosmin which is found in the cytoplasm of AML patients with variable prevalence and proven to have prognostic signifi cance. It is involved in several activities at cellular level such as ribosomal biosynthesis, maintenance of genome stability and molecular chaperon functions. It causes inactivation of tumor suppressor gene p53. Th is mutation seem to identify patients that respond better to chemotherapy hence this study will help to identify patients with good prognosis. Its association with FLT3 is related to poor outcome. Objectives: To evaluate the frequency of NPM1 gene mutation in newly diagnosed patients of AML. Study Design: Cross Sectional Study. Settings and Duration: Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st September 2014 to 30th June 2015. Patients and Method: Patients of all age groups and gender diagnosed with AML at AFIP were included. Aft er informed consent 2ml bone marrow samples were collected from patients. RNA was extracted using triazole reagent kit and complimentary DNA was synthesized using reverse transcriptase. Polymerase chain reaction (PCR) was done using Amplifi cation refractory mutation system methodology. A 320 base pair fragment was amplifi ed from 1micro litre of complimentary DNA in a total volume of 25 micro liter of the reaction mixture containing 10 pmol of each primer, NPM-A and NPM-REV 6, 1x PCR buff er, 2.5mmol/L Magnesium Chloride, 5 mmol/L deoxynucleoside-5-triphosphate and 0.7U of Taq polymerase.PCR products will be visualized by electrophoresis on Poly Acryl amide Gel. Results: Out of 90 AML patients 34 (37.7%) were positive for NPM1 gene mutation with a median age of 37 years. 25 (73.5%) were males while 9 (26.4%) were females. Out of 34 NPM1 positive patients 14 patients (41%) were AML M2 subtype, 13 patients (38.2%) were AML M4, 4 cases (11.7%) were AML M3 while there were 2 cases (5.8%) of AML M5a. Out of 7 FLT3 positive cases 1 was positive for NPM1 mutation as well. Aft er induction therapy with D3 A7 (Daunoblastine :45 to 90mg/m2 and Cytosar 100-200mg/m2 Day 1 to Day 7) 79% of these NPM1 positive patients achieved remission. Conclusion: NPM1 gene mutation is quite frequent in our patients of AML and is associated with good response to chemotherapy.