The diagnosis of hematologic malignancies is not a straightforward procedure. There are many specialisms required to undertake morphological analysis, flow cytometry, cytogenetic, and molecular genetic analyses.
In an article published in Blood, Richard Dillon and the late David Grimwade from King’s College London provide an expert commentary on the work by McKerrell et al. relating to a novel Next-Generation Sequencing (NGS) platform. McKerrell and his colleagues developed and validated Karyogene, a comprehensive one-stop diagnostic platform for the genomic analysis of myeloid malignancies. According to Dillon and Grimwade, this novel platform can identify point mutations, common fusion genes and copy-number alterations in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) from a single genomic DNA sample.
McKerrell et al. validated this method against 62 AML, 50 MDS and 40 blood DNA samples from individuals without evidence of clonal blood disorders.
Their key findings demonstrated detection of sequence changes in 49 genes, including the prognostically important but difficult to identify FLT3-ITD mutation. In addition, there was the robust detection of all occurrences of one of the four common AML-associated translocations, namely t(15;17)/PML-RARA (9/9), inv(16)/CBFB-MYH11 (8/8), t(8;21)/RUNX1-RUNXT1 (4/4), and MLL fusions (8/8). The study was published in Blood in 2016.
Grimwade and Dillon conclude that, while this novel platform is very promising for the future of diagnosis of hematological malignancies such as AML, there are still some caveats regarding the use of the NSG based diagnostic tool. They state that in order to fully maximize diagnostic potential of this platform, it is necessary for RNA (as well as DNA) to be routinely extracted at diagnosis in order to provide baseline samples that allow molecular monitoring of Minimal Residual Disease.
Please find the full commentary by Grimwade and Dillon in Blood here.