The frequency of Nucleophosmin1 gene mutation in newly diagnosed patients of Acute Myeloid Leukaemia

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Muhammad Ayyub

Armed Forces Institute of Pathology, Pakistan

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

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 significance. 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. This 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. After 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 Amplification refractory mutation system methodology. A 320 base pair fragment was amplified 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 buffer, 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. After 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.

Biography :

Major General Professor Dr Muhammad Ayyub, completed his PhD from University of London in 1993 and qualified MRC Path in 1994. He was awarded FRC Path in 2002. He is a teacher par excellence with a large number of publications in reputed journals to his credit. He is serving on the editorial boards for Pakistan, Journal of Pathology, Pakistan Armed Forces Medical Journal, Foundation University Medical Journal and Member technical committee Pakistan Medical & Dental Council Islamabad. He has held the highest professional appointments in Armed Forces, Advisor in Pathology (Armed Forces), Professor of Pathology, Army Medical College, Dean Faculty of Pathology College of Physicians and Surgeon of Pakistan, President Pakistan Society of Haematology and presently he is working as Commandant Armed Forces Institute of Pathology Rawalpindi (Pakistan).

Email: drayyub57@yahoo.com