Distribution of PML-RARA isoforms in Acute promyelocytic leukemia patients from a tertiary hospital in KZN, South Africa using qPCR.
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Date
2017
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Abstract
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.
Description
Masters Degree. University of KwaZulu-Natal, Durban.