Importance of FISH combined with Morphology, Immunophenotype and Cytogenetic Analysis of Childhood/ Adult Acute Lymphoblastic Leukemia in Omani Patients

Abstract

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic andprognostic information with a direct impact on patient management. Detection of chromosome abnormalities byconventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant rolein assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition ofgenetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the lasttwelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomalabnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital.G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% ofcases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidygroup (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidygroup (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) withabnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed byt(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application ofthe FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis withALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomalaberrations along with non-specific rearrangements and their association with specific immunophenotypes. Thisstudy pool is representative of paediatric/adult ALL patients in Oman.