Detection of Common Chimeric Fusion Transcripts in Acute Lymphoblastic Leukemia (ALL) Patients Using Multiplex Reverse Transcriptase Polymerase Chain Reaction Assay: A North Indian Tertiary Care Centre Experience

Chromosomal abnormalities constitute an important parameter to identify prognostically relevant subgroups in acute lymphoblastic leukemia (ALL). Many western studies report the incidence of common chimeric fusion transcripts as 30–35%, however the data regarding the Indian patients is very scarce.

The aim of the present study was to detect presence of common chimeric fusion transcripts of t(12;21), t(9;22), t(1;19) and t(4;11) in adult and pediatric ALL cases using the Multiplex RT-PCR assay.

This prospective study included 100 consecutive ALL cases diagnosed during last one year; 54 patients were <12 years of age. Diagnosis of ALL was made on the basis of bone marrow (BM) examination and flowcytometric immunophenotypic (FCM-IP) analysis. Approximately 2 ml of peripheral blood (PB) sample or 0.5 ml of BM sample was collected in EDTA. RNA extraction and cDNA synthesis was performed using commercial kits, according to standard protocols. RT-PCR assay was carried out using primers specific to the fusion transcripts of TEL-AML1 t(12;21); BCR-ABL t(9;22); E2A-PBX t(1;19) and MLL-AF4 t(4;11). The results of RT-PCR and FCM-IP were blinded and compared later.

Out of the 100 cases enrolled in the study, 54% were pediatric and 46% adult cases. Among the pediatric ALL cases, 49 were diagnosed as B-lineage ALL, 3 T-lineage ALL and 2 Biphenotypic ALL. Whereas among the adult ALL cases, 30 were diagnosed as B-lineage ALL, 12 T-lineage ALL and 4 Biphenotypic ALL. A total of 26% showed positivity for various fusion transcripts: 13% each pediatric and adult cases being positive. Of the 12 positive pediatric B-lineage ALL cases, 8 were positive for TEL-AML1 transcripts, 1 for BCR-ABL transcripts, 1 for E2A-PBX transcripts and 2 for MLL-AF4 transcripts. Out of the 11 positive adult cases, 7 were positive for BCR-ABL transcripts, 2 were positive for TEL-AML1 transcripts and 1 each for E2A-PBX transcripts and MLL-AF4 transcripts. BCR-ABL transcripts were detected in 1 out of 2 pediatric biphenotypic ALL and 2 out of 4 adult biphenotypic ALL cases. None of the pediatric cases was positive for the MLL-AF4 transcripts. None of the 4 transcripts were detected in any T-lineage ALL.

Results of our study are comparable to those of other western and Asian studies, with TEL-AML1 transcripts being the most common fusion transcripts seen in pediatric B-ALL cases and BCR-ABL in adult cases. However two Indian studies had reported much lower incidence of TEL-AML1 and MLL-AF4 transcript in B-ALL cases. Identification of good prognostic groups and rationalization of therapy assumes great importance in our set ups as many patients are economically under-privileged. Relationship of these transcripts to the prognosis of our ALL patients will be evaluated in future.

No relevant conflicts of interest to declare.