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


OBJECTIVE
To study different PML-RARα bcr isoforms in Indian patients and to find any correlation with various haematological parameters and response to treatment.


METHODS
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
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.


METHODS
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.
Professor & Head of Department, Department of Immunohematology and Transfusion Medicine, Armed Forces Medical College, Pune, India.
Tathagata
T
Chatterjee
Senior Resident, Department of Pathology, NDMC Medical College, Delhi, India.
Srishti
S
Gupta
Associate Professor, Department of Haematology, Army Hospital(R & R, Delhi, India.
Sanjeevan
S
Sharma
Associate Professor, Department of Pathology, Army Hospital(R & R), Delhi, India.
Prosenjit
P
Ganguli