Precision medicine initiative uses whole genome sequencing to identify novel prognostic signatures and the impact of genomic subgroups in MDS allogeneic HCT patients
With two studies presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, the National Marrow Donor Program® (NMDP)/Be The Match® called attention to its precision medicine initiative. Researchers presented novel prognostic signatures in allogeneic hematopoietic cell transplantation (HCT) patients with myelodysplastic syndrome (MDS) based on whole genome sequencing and examined the impact of genomic subgroups on survival.
MDS represent a diverse group of myeloid malignancies characterized by cytopenia and increased risk of progression to acute myeloid leukemia (AML) driven by accumulated somatic genetic mutations in hematopoietic stem cells (HSCs). While recurrent mutations are known to associate with adverse outcomes in MDS, 10% of MDS cases have no known genetic indicators for survival prognosis. Whole genome sequencing detects comprehensive mutations on coding and non-coding regions that empowers discovery of novel genetic biomarkers. This work facilitates the adoption of precision medicine tactics that can allow for more specific and tailored treatment.
NMDP/Be The Match launched a precision medicine initiative to evaluate novel methods to characterize disease risk and post-transplant prognosis in MDS through the CIBMTR® (Center for International Blood and Marrow Transplant Research®) with funding support from the Office of Naval Research. The CIBMTR is a research collaboration between NMDP/Be The Match and Medical College of Wisconsin. To date, a cohort of approximately 600 allogeneic donor recipient pairs with pre-transplant research samples available through the CIBMTR Research Repository have been whole genome sequenced and evaluated for genomic methylation patterns (chemicals the body uses to turn genes on or off). These genomic data in combination with the longitudinal clinical outcomes data collected through the CIBMTR Research Database are being studied to gain insights into the MDS disease process and contributions of both donor and recipient genetic diversity to transplant outcomes.
The goal of these studies is to ensure that the right patient receives the right therapy at the right time while limiting unnecessary toxicity. The initiative has reported several novel findings regarding the contribution of somatic mutations in MDS disease that are prognostic for outcomes post-transplant, as seen in the data presented at ASH. These studies will provide insights into which patients are likely to respond to transplant therapy and help identify new targets for potential curative interventions. For example, identification of cancer characteristics indicative of a high likelihood of relapse post-transplant could be used for monitoring disease reoccurrence and timing of administration of a cellular therapy.
Study BIO21-03: Zhang T, et al., ASH poster presentation abstract
Study BIO20-08: Zhang T, et al., ASH poster presentation abstract
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