DISTRIBUTION OF DIFFERENT PML/RARΑ BCR ISOFORMS IN INDIAN ACUTE PROMYELOCYTIC LEUKAEMIA (APL) PATIENTS AND CLINICOHEMATOLOGICAL CORRELATION

Abstract

Context: Acute promyelocytic leukemia (APL), an  AML subtype, is characterized  morphologically by abnormal promyelocytes. Molecular studies show three possible bcr isoforms of PML- RARα fusion gene . This study undertakes analysis of PML-RARα bcr isoforms and their correlation with  hematological parameters  and  response to treatment in Indian patients. Aims: To study different bcr isoforms in Indian patients and to find any correlation with various hematological parameters and response to treatment Settings and Design: Patients diagnosed as APL on morphology or flowcytometry and confirmed by RQ PCR were  included in the study. Treated APL patients or patients with relapse and  on follow up were excluded from the study. Methods and Material:   Twenty  patients over  thirty one months  period were included. The clinical, hematological & morphological features were analysed, the latter using  routine & special cytochemical stains on    blood and bone marrow . Flow cytometric evaluation  using 4-color Beckman Coulter FC 500  and  molecular studies  using RT PCR FusionQuant® kits for bcr-1, bcr-2  and  bcr-3 on the instrument  Rotor Gene™ 3000 were  performed . Statistical analysis used: Student t test was applied to correlate different bcr isoforms with various haematological parameters and response to treatment. Results: In our study , M:F ratio was 1.5:1 with  median age  42 years, Hb - 8.0 g/dl,  TLC-7900/μl, and platelet – 35000/ μl and varied clinical presentation. Four patients were microgranular variants and rest  hypergranular . MPO and CAE  positivity was   100% and 33.33% for NSE. Molecular analysis revealed bcr1 in 42.85% , bcr2 in 14.28% and bcr 3 in 38.09 % patients. No correlation was found between bcr isoforms , different hematological parameters and response to treatment. Conclusions: Higher incidence of bcr-1 was found in Indian APL patients with no significant correlation between different hematological parameters and response to treatment.