Evaluation Of The AMLprofiler in The South African Context: Report On Preliminary Findings

Acute myeloid leukaemia (AML) is typified by diverse genetic abnormalities and marked heterogeneity in both response to treatment and survival. Diagnosis is made according to a World Health Organisation classification system, whereby clinicians are able to categorise cases into favourable, intermediate and poor risk groups. This has recently been augmented by several novel molecular biomarkers, such as genetic alterations of NPM1 and CEBPA that infer a favourable prognosis, and increased expression levels of BAALC and EVI1 that infer an unfavourable prognosis.

Molecular investigations for the prognostic stratification of AML are limited in South Africa, and only FLT3 and NPM1 variants are requested for a minority of cases. The AMLprofiler^TM from Skyline Diagnostics is a novel diagnostic microarray that incorporates seven molecular variables used to predict post therapy survival rates. The goals of the study are to evaluate the benefits of the AMLprofiler^TM in the South African setting.

Bone marrow was collected from patients diagnosed with de novo AML, based on a blast count of greater 20%, and material was submitted for routine cytogenetic, FISH and molecular testing. Although the AMLprofiler^TM is not indicated for diagnostic use on peripheral blood, matching samples were collected where possible, and also in cases where clinicians were unable to obtain bone marrow from patients. RNA was isolated within 48 hours of collection and the samples prepared for analysis on an Affymetrix microarray platform (GeneChip® System 3000Dx v.2). Results were investigated for concordance with routine testing methods and value-add with respect to cost, time and the personnel required. Samples from both the public and private sectors are being collected, for which logistical aspects differ significantly and are considered for the comparisons.

A total of 65 AML patient samples are planned for collection, of which 50 will be from bone marrow and 15 from peripheral blood. To date, 22 samples have been assayed to completion and reported. The sample thus far is comprised of 68% Caucasian and 32% Black African samples; 72% male and 25% female; 90% from the public sector and 10% from private. Results indicate that several samples were determined to be positive for molecular biomarkers not routinely investigated in South Africa, including CEBPA, BAALC and EVI1. Interestingly, none of the samples were reported to harbour the favourable prognostic marker NPM1, which is reported globally at frequencies ranging from 25-40%. Reporting via standard approaches varies in cost and time to result, which ranges from five to 27 days. Implementation of the AMLprofiler^TM would offer an opportunity to report in a consistent manner and price, and in a more reliable time frame.

Preliminary data indicates benefit for use of AMLprofiler^TM in South Africa, and would allow for improved risk stratification of patients with AML. The comprehensive nature of the microarray and the considerable decreased time to result are factors that could potentially lead to more rapid initiation of appropriate therapy for patients with AML.