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Browsing School of Clinical Medicine by Subject "Acute Promyelocytic Leukemia."

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    Distribution of PML-RARA isoforms in Acute promyelocytic leukemia patients from a tertiary hospital in KZN, South Africa using qPCR.
    (2017) Safiya, Ebrahim.; Gordon, Michelle Lucille.; Parsanath, Sharlene.
    The study of genetic epidemiology of cancers in Africa is unique as compared to first world countries, as it entails the combination of gene-environment interaction, poor socio-economic conditions and the high prevalence of infectious (e.g. tuberculosis and HIV) and non-infectious diseases. Acute Promyelocytic Leukemia (APL), a subtype of Acute Myeloid leukemia (AML) if not diagnosed within 24 hours because of its hemorrhagic tendencies, becomes a medical emergency. It has become one of the most treatment-responsive cancers due to its excellent response to all trans-retinoic acid (ATRA). Advances in molecular diagnostics have resulted in a reversetranscriptase polymerase chain reaction (RT-PCR) test to detect the PML-RARA (retinoic acid receptor alpha) transcript found in APL’s. Globally, many centers have investigated the different breakpoint cluster regions (bcr) to classify the patients into different prognostic groups for specific molecular targeted treatment. However, there are no reports from Africa on the frequency of the different isoforms in APL patients. In this study we aim to identify and determine the frequency of bcr isoforms in APL patients from a tertiary hospital in Kwa Zulu Natal (KZN) by quantitative RT-PCR (qPCR). The correlation of the hematological parameters with the different isoforms was analyzed by descriptive non-parametric statistical analysis. The qPCR confirmed bcr1 to be the predominant isoform (63,6%) followed by bcr3 (31,8%) and bcr2 (4,5%). There was a median age group of less than 45 in our patient cohort. Patients with the bcr3 isoform had a poor prognosis according to their clinical risk stratification but this did not necessarily result in poor overall survival when monitored for minimal residual disease (MRD). The HIV-infected APL patients with different isoforms responded to “standard of care” treatment in the same way as noninfected HIV patients.