Cytogenetic and Molecular Genetic Studies on Indian Patients with Leukemia Detection of Minimal Residual Disease

Abstract

The present investigation was designed to study cytogenetic and molecular genetic aspects of leukemia patients among Indian population and for the first time to detect minimal residual cells in CML patients during the course of therapy. A total of 49 patients with leukemia diagnosed as per FAB criteria were analyzed. The incidence of leukemia was more in males (65.3%) than in females (34.7%). The incidence of CML is high (34.7%) compared to other hematological malignancies. Thirty five percent of CML patients are found to have hepatospleno megaly and lymphadenopathy. ALL patients with hyperdiploidy of around 60 chromosomes revealed better prognosis and survival period. Trisomy 12 was observed in 40% of CLL patients Translocation (9;22) (q34;q11) (ph1 chromosome) was observed in 15 (88.2%) out of 17 CML patients analyzed. For the first time, we studied the p53 deletion and c-myc amplification by FISH in Indian patients with leukemia. p53 was deleted in a CML patient who exhibited isochromosome 17 and this is associated with the progression of the disease in CML patients. Three AML patients and one CML patient showed c-myc amplification. c-myc amplification was associated with the poor prognosis. 66 PCR results suggests that ras oncogene mutation was observed in 2 out of 17 patients analyzed. ras oncogene mutation seem to occur in the late stage of the disease and contributed to transformation to the blast phase in CML patients. For the first time, we followed-up the CML patients, to detect minimal residual cells by FISH in the bone marrow and/or peripheral blood during the course of chemotherapy. The reduction of ph1 chromosomes during the course of therapy was achieved by FISH. The reduction of ph1 chromosome during therapy showed poor prognosis in blast crisis. The detection of residual leukemia cells at a level of 1 - 2% indicates that FISH is reliable, sensitive and specific diagnostic method for detection of MRD in CML patients. newline