American Society of Hematology

Enhancing Genomic Profiling of Blood Diseases

Molecular profiling of DNA and RNA has provided valuable new insights into the genetic basis of non-malignant and malignant hematologic disorders as well as an increased understanding of basic mechanisms that regulate hematopoiesis. The increasingly widespread use of genome sequencing and genomic profiling has significantly improved the diagnoses and treatment of hematologic diseases by identifying unique variants that can be targeted with gene-based targeted therapeutic approaches.

ASH has an enduring interest in enhancing genomic profiling of all hematologic diseases. This is evident in the Society’s programs and activities supporting this research priority and in the creation of a dedicated Task Force on Precision Medicine aimed at improving the use of molecular data in clinical care, research, and education.

The Society’s efforts can be categorized in the following key themes:

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.

ClinGen Partnership

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.

Because of the rarity of samples from hematologic disorders, there are often insufficient numbers to carry out statistical validation of sequencing results. ASH is interested in improving existing genomic data storage, sharing, and analysis platforms by populating them with existing NGS data from hematologic samples.

ASH is assisting its membership with deposition of data sets from malignant diseases to the National Cancer Institute's Genomic Data Commons (GDC), a repository for genomic sequence data annotated with phenotype and clinical information. The GDC also provides tools for analysis across cancer studies.

ASH is currently engaged in a pilot for the deposition of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) studies, with others soon to follow. The genomic data deposition efforts will be leveraged to support ASH’s research registry, with the goal of enabling hematologists to carry out research questions across both clinical and genomic information.

If you have data sets you wish to deposit into the GDC, please contact ASHPrecisionMedicine@hematology.org.

ASH is committed to enhancing the scientific understanding of precision medicine. In July 2017, the Society published a Precision Medicine Review Series in its journal Blood. The review series covers the most pressing topics in precision medicine, including those listed below.

ASH Task Force on Precision Medicine

  • Ken Anderson, MD, Dana-Farber Cancer Institute
  • Emery Bresnik, PhD, University of Wisconsin
  • John Byrd, MD, The Ohio State University
  • Ben Ebert, MD, PhD, Harvard Medical School
  • Willem Fibbe, MD, PhD, Leiden University Medical Center
  • Lucy Godley, MD, PhD, The University of Chicago
  • Torsten Haferlach, MD, Munich Leukemia Laboratory
  • Michael Hallek, MD, University of Cologne
  • Ross Levine, MD, Memorial Sloan Kettering Cancer Center
  • Charles Mullighan, MBBS, MD, St. Jude Children's Research Hospital
  • Grzegorz Nowakowski, MD, Mayo Clinic – Rochester
  • Willem Ouwehand, MD, PhD, University of Cambridge
  • Sophie Paczesny, MD, Indiana University
  • Steven Pavletic, MD, National Cancer Institute, National Institues of Health
  • Andrew Roberts, MBBS, PhD, Walter & Eliza Hall Institute of Medical Research
  • Margaret Shipp, MD, Dana-Farber Cancer Institute
  • Akiko Shimamura, MD, PhD, Boston Children's Hospital
  • David Steensma, MD, Dana-Farber Cancer Institute
  • Kimberly Stegmaier, MD, Dana-Farber Cancer Institute
  • Jeffrey Tyner, PhD, Oregon Health & Science University
  • Matthew Walter, MD, Washington University in St. Louis

Somatic Working Group Members

  • Rafael Bejar, MD, PhD, University of California – San Diego
  • Ben Ebert, MD, PhD, Harvard Medical School
  • Torsten Haferlach, MD, Munich Leukemia Laboratory
  • Michelle LeBeau, PhD, The University of Chicago
  • Elaine Mardis, PhD, Washington University
  • Charles Mullighan, MBBS, MD, St. Jude Children's Research Hospital
  • Akiko Shimamura, MD, PhD, Boston Children's Hospital
  • David Steensma, MD, Dana-Farber Cancer Institute
  • Matthew Walter, MD, Washington University in St. Louis
  • Jinghui Zhang, PhD, St. Jude Children's Research Hospital

Germline Working Group Members

  • Emery Bresnik, PhD, University of Wisconsin
  • Ben Ebert, MD, PhD, Harvard Medical School
  • Lucy Godley, MD, PhD, The University of Chicago
  • Torsten Haferlach, MD, Munich Leukemia Laboratory
  • Marshall Horwitz, MD, University of Washington
  • Charles Mullighan, MBBS, MD, St. Jude Children's Research Hospital
  • Kim Nichols, MD, St. Jude Children's Research Hospital
  • Willem Ouwehand, MD, PhD, University of Cambridge
  • Sharon Plon, MD, PhD, Baylor College of Medicine
  • Akiko Shimamura, MD, PhD, Boston Children's Hospital

Questions?

For additional information about ASH’s precision medicine activities, please contact ASHPrecisionMedicine@hematology.org.

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