Characterization of chromosomal abnormalities in acute myeloid leukaemia patients at the university teaching hospital, Lusaka, Zambia

Abstract

Acute myeloid leukaemia (AML) is a highly malignant clonal hematopoietic disease caused by both inherited and acquired genetic alterations. Current AML classification and prognostic systems incorporate genetic information but are limited to known abnormalities that have previously been identified with the use of cytogenetics, array comparative genomic hybridization (CGH), gene-expression profiling, and the resequencing of candidate genes. At diagnosis, most patients with AML harbour at least 1 chromosome aberration in their marrow blasts. With the targeted cytogenetic therapy, 30% of the patients achieve long-term cure. At University Teaching Hospital(UTH) however, the current diagnostic approach of acute leukaemia involves mainly cytomorphology and occasional flow cytometry. The cytomorphological blast characterization is not enough to provide a critical determination of prognosis and developing a treatment plan. Most of the AML patients at UTH die within few months after diagnosis despite being put on chemotherapy. To characterize AML according to WHO 2008 revised classification in patients at the University Teaching Hospital. This was a descriptive cross-sectional study conducted to characterize acute myeloid leukaemia (AML) according to WHO 2008 revised classification in patients at the UTH. Patients with AML were simultaneously analyzed for the presence of 4 genetic abnormalities, PML/RARα for t(15;17), AML1/ETO for t(8;21), CBFβ/MYH11 for inv(16)/t(16;16) and rearrangements of the MLL gene for 11q23 abnormalities. AML was classified using the new World Health Organization (WHO) classification for haematologic malignancies. The techniques used were standardized according to the recommendations of the European BIOMED-1 Concerted Action. The overall frequency of leukemia displaying one of the four recurrent cytogenetic translocations were 13 cases (46.5%) of which PML/RARα transcript was present in six(6) patients (21.4%) (3 were bcr1, 1 bcr2 and 2 bcr3). The AML1/ETO fusion transcript was detected in only one(1) case (3.6%) with M2 morphology, but other cases with M2 morphology were negative. CBFβ/MYH11 transcript was present in 2 cases (7.1%) and some of them displaying M4Eo morphology. Finally, 4 cases (14.3%) showed rearrangements of the MLL gene. By contrast, the frequency of AML not otherwise characterized which was 15 cases (53.6%) increased with age (13% for 6-35years age group, 20% for 36-65years age group and 67% for above 66years age group). Our results differ from those reported from the United States and North/Central Europe, particularly regarding the incidence of t(15;17) and t(8;21) translocations. In Zambia the frequency of t(15;17) is higher while that of t(8;21) is lower. This supports the view that geographic variations in tumor-associated aberrations in hematologic malignancies exist. Our study showed that chromosomal alteration PML/RAR t(15,17) which was 21.4% ,was the commonest, whereas AML1/ETO t(8,21) which was 3.6%,was the least common among patients presenting at UTH, Lusaka, Zambia. Our study showed that

chromosomal aberration detected in our patients make them less responsive to cytotoxic drugs. The use of molecular technique at point of diagnosis would assist in identifying AML with better prognosis by administering appropriate treatment. The results support the existence of chromosomal abnormalities of AML in our Zambian patients. Awareness of these chromosomal abnormalities and morphology could contribute to the design of cost-effective screening strategies, adapted by our National Health systems according to the prevalence of locally detected genetic aberrations. Key Words: Acute myeloid leukaemia (AML)