A Study of Incidence of Recurrent Genetic Translocations in Adult and Pediatric Acute Lymphoblastic Leukemia (ALL) Patients in North India
Acute lymphoblastic leukemias (ALL) are characterized by various distinctive chromosomal/molecular abnormalities, having important diagnostic and prognostic implications. Many western studies quote the incidence of fusion transcripts to be 30-35% in ALL. However the data from Indian sub-continent is scarce. Studies in different population groups are needed to better characterize/categorize these abnormalities and to design appropriate treatment protocols. Strategies for molecular monitoring of minimal residual disease (MRD) in ALL cases are also designed according to these abnormalities.
METHODS:
Present study was undertaken from May 2010 to July 2013, enrolling all cases diagnosed as ALL by morphology and flow cytometry immunophenotyping. Common fusion transcripts, including TEL-AML1 [t(12;21)]; BCR-ABL [t(9;22)]; E2A-PBX1 [t(1;19)] and MLL-AF4 [t(4;11)] were tested with a single multiplex RT-PCR assay. Incidence of translocations was determined in ALL cases.
RESULTS:
397 cases of ALL were tested for above mentioned fusion transcripts, of which 127 (32%) were adults and 270 (68%) children, with a male:female ratio of 1.9:1. Overall, 70 (17.6%) cases were positive for any of the fusion transcripts; of these, 25 were adult and 45 pediatric patients. The most common fusion transcript was TEL-AML1, detected in 28 (7.1%) cases, followed by BCR-ABL in 27 (6.8%) cases.
Adult ALL- Of the 127 cases, 25 (19.7%) were positive for any one fusion transcripts, with BCR-ABL being most common, detected in 14/127 (13.7%) cases.
Pediatric ALL- Of the 270 cases, 45 (20%) were positive for any one fusion transcripts, TEL-AML1 was most common detected in 22 (8.2%) cases.
Overall reported incidence of transcripts in adult and pediatric ALL from studies in different parts of world ranges from 16.7% to 50% and 8.6% to 33.35, respectively.
CONCLUSIONS:
The overall incidence of fusion transcript was 17.6% which was lower than that reported from western countries. This observation could result from certain ethnic, genetic and environmental factors. However, there was no significant difference in the incidence of occurrence of recurrent genetic translocations between adult and pediatric ALL cases, which is comparable to studies from western countries which have also not reported differences between adult and pediatric patients.
TEL-AML1 [t(12;21)], indicating good prognosis, was the most frequent fusion transcript. Rest of the fusion transcripts are associated with worse prognosis.
We are in the process of generating a database of hematological malignancies, incorporating demographic, hematological, cytogenetic/ molecular genetic features in north India.