Increasingly, there are more technologies available to hematologists, such as next generation sequencing (NGS), that can be applied not only in research but also in a diagnostic setting by physicians. NGS allows researchers and clinicians to detect genetic mutations that could be associated with disease progression (e.g., carrying out genomic profiling of patient samples). While many mutations have been documented, few have undergone rigorous literature and experimental review as part of curation practices to indicate causation, not just correlation to disease.
To help assign clinical significance to these mutations, ASH has created a partnership with a leading curation resource funded by the National Institutes of Health (NIH) Clinical Genome Resource (ClinGen). This resource has developed standardized methods for defining the clinical relevance and actionability of genes and variants; it has also standardized clinical annotation and interpretation of variants by expert panels. ASH is collaborating with ClinGen to support two expert panels for curation of germline mutations for predisposition to myeloid malignancies and platelet disorders. These efforts will be led by Lucy Godley, MD, PhD, of The University of Chicago and Jorge DiPaola, MD, of the University of Colorado.
Once variants are curated and are publicly available, this resource will provide hematologists with confidence as to whether certain mutations indeed play a role in disease, which can alter a diagnosis or a course of treatment.
Hematology Profiling Consortium
In parallel efforts, and supported by surveys of ASH membership, the Task Force on Precision Medicine is interested in addressing unmet needs in genomic profiling of malignant and non-malignant hematologic diseases. These efforts will contribute to increasing the amount of genomic profiling by NGS carried out on patients with hematologic diseases, especially in diseases that are extremely rare and for which such sequence information may not exist.
Based on feedback from its members, ASH is aware of many thousands of existing samples that could answer important scientific or clinical questions, if sequenced. ASH is interested in establishing partnerships with the public and private sector to support a hematology profiling consortium. The consortium will support whole genome, whole exome, RNA, and bisulfite sequencing of existing and possibly future prospective samples from patients with hematologic diseases. In addition, this private-public partnership will develop standards for consistent sample processing, data capture, and annotation with clinical information.
ASH is seeking partners who can assist with sequencing, bioinformatics support, and a hematology-focused data dictionary. The relationships will be formalized either through existing contracting mechanisms or through in-kind contributions from consortium partners.
If you are interested in partnering with ASH, please contact ASHPrecisionMedicine@hematology.org.