Distribution of Different PML/RARα bcr Isoforms in Indian Acute Promyelocytic Leukemia (APL) Patients and Clinicohematological Correlation

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 haematological parameters and response to treatment in Indian patients. AIMS: To study different PML-RARα bcr isoforms in Indian patients and to find any correlation with various haematological 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, haematological & 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 Fusion Quant® kits for bcr-1, bcr-2 and bcr-3 of PML-RARα bcr isoforms 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 the rest were hypergranular. MPO and CAE positivity were100% and for NSE it was 33.33%. Molecular analysis revealed PML-RARα isoforms of bcr1 in 42.85%, bcr2 in 14.28% and bcr3 in 38.09% patients. No correlation was found between PML-RARα bcr isoforms, different haematological parameters and response to treatment. CONCLUSIONS: Higher incidence of PML-RARα bcr-1 isoform was found in Indian APL patients with no significant correlation between different haematological parameters and response to treatment.