Characterization of the immunophenotypic aberrancies with respect to common fusion transcripts in B-cell precursor acute lymphoblastic leukaemia - a report of 986 Indian patients.

Objective Based upon the immunophenotype, acute lymphoblastic leukaemia (ALL) can be categorized into B or T cell lineage (B-cell ALL or T-cell ALL). B-cell precursor ALL (BCP-ALL) cases show various genetic/molecular abnormalities and varying frequencies of chimeric fusion transcripts in BCP-ALL cases are reported from different parts of the world. We studied the immunophenotypic aberrancy profiles of a large number of BCP-ALL cases with respect to various common chimeric fusion transcripts. Materials and Methods Flowcytometric Immunophenotyping and Multiplex RT-PCR assay were performed in 986 BCP-ALL cases. Results Among 986 BCP-ALL cases, the incidence of various fusion transcripts was 38.36% in adult cases and 20.68% in pediatric cases. Adult BCP-ALL cases harbouring t(9;22)(BCR-ABL1) fusion transcripts and having expression of aberrant myeloid markers, were significantly older at presentation (age, p=0.0218) and had male preponderance (male, p=0.0246), as compared to those without aberrant myeloid expression. In pediatric cases expressing t(12;21)(ETV6-RUNX1) chimeric fusion transcript, aberrant expression of CD13 was observed in 39.13%, CD33 in 36.95% and CD117 in 8.69% patients respectively. Pediatric BCP-ALL cases harbouring ETV6-RUNX1 fusion transcript and having expression of aberrant myeloid markers were not significantly different as compared to those without, with respect to their demographic and clinico-hematological characteristics (p=0.5955). Aberrant myeloid markers were rarely/never expressed in pediatric and adult BCP-ALL patients harbouring t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts. Conclusion Aberrant myeloid markers were frequently expressed among BCP-ALL patients harbouring t(9;22)(BCR-ABL1) and t(12;21)(ETV6-RUNX1) fusion transcripts. However BCP-ALL patients harbouring t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts rarely/ never expressed aberrant myeloid markers. Aberrant myeloid CD markers can be used in predicting chimeric fusion transcripts at baseline, so as to plan desirable TKI therapy in BCP-ALL cases with specific chimeric fusion transcripts. This study delineates the relationship of chimeric fusion transcripts with the aberrant expression of myeloid markers in a large cohort of BCP-ALL cases.