NEW YORK (GenomeWeb) – The Association of Molecular Pathology has published recommendations to help guide management of patients with chronic myeloid neoplasms.
The recommendations, published this week in the Journal of Molecular Diagnostics, call for including a minimum of 34 specific genes in targeted sequencing panels.
The AMP CMN working group "recognized a clear unmet need for evidence-based recommendations to assist in the development of the high-quality pan-myeloid gene panels that provide relevant diagnostic and prognostic information and enable monitoring of clonal architecture," Rebecca McClure, an associate professor at the Northern Ontario School of Medicine and a co-lead author of the study, said in a statement.
Because there are multiple forms of CMNs, including myelodysplastic syndromes and myeloproliferative neoplasms, there is a lot of variability in the genes that are currently included on targeted next-generation sequencing panels used to diagnose or manageme patients, the authors wrote.
The AMP working group thus reviewed more than 600 published studies relating to DNA variants in all forms of adult CMNs that were not chronic myeloid leukemia, and including the syndromes clonal hematopoiesis of indeterminate origin and clonal cytopenia of undetermined significance, which involve having variants in myeloid genes without clinical features of a myeloid neoplasm.
The goal was to "provide education and guidance regarding the practical clinical relevance of variants in this group of neoplasms," the authors wrote, with the idea that a "collation of genomic biomarker information in CMNs would be beneficial for those involved in the clinical laboratory evaluation and management of such patients."
In reviewing the literature, the group used the World Health Organization's classification system for CMN and developed a database that included the genes identified, the variants related to the various WHO disease categories, and other factors of diagnostic, prognostic, or therapeutic relevance. In addition, the group included gene function and whether it was associated with other genes.
The group then focused on genes that were found in 10 percent or more of cases to develop their list of 34 genes. Those genes "appear to be the most important biomarkers based on our current understanding of CMNs," the authors wrote.
The majority of genes in the list fall into four key pathways: receptor kinase signaling transduction, transcription, epigenetic medication, and RNA splicing.
In addition, the group reported that while CMNs are complex and heterogeneous, there are also many similarities. For instance, they reported that in most cases, the founding variant is a gene involved in either epigenetic regulation or RNA splicing. And, alterations that occur later in disease progression tend to be the ones that drive the heterogeneous features that are often used to subtype CMNs.
The authors noted that their 34-gene list does not include all variants that could be detected in all types of myeloid neoplasms such as acute myeloid leukemia, and that laboratories developing pan-myeloid panels should consider the genes to be a "minimum recommended list to provide relevant diagnostic and prognostic information in CMNs and enable monitoring of clonal architecture."