Scientific Committee on Myeloid Neoplasia
Lucy Godley, MD,PhD ('17)
Ravi Majeti, MD, PhD ('17)
Rebecca Chan, MD, PhD ('18)
Konstanze Dohner, MD ('19)
Stephanie Halene, MD ('20)
Soheil Meshinchi, MD, PhD ('18)
Ann Mullally, MD ('20)
Satu Mustjoki, MD,PhD ('19)
Vivian Oehler, MD ('17)
Matthew J. Walter, MD ('17)
The Scientific Committee on Myeloid Neoplasia is focused on the biology and treatment of myeloid malignancies. Underlying the Committee’s emphasis on the pathobiology of malignancies involving the myeloid lineage is the premise that clarifying the basic mechanisms of myeloid neoplasia will lead to more effective and less toxic treatments. There is an increasing awareness of the heterogeneity of myeloid malignancies demanding rational and adapted therapies. Pediatric and adult as well as acute and chronic myeloid malignancies are areas of interest.
Biological/mechanistic areas of interest
Aberrant genetic and epigenetic changes contribute to myeloid leukemogenesis. Many of these molecular abnormalities affect myeloid differentiation, proliferation, and senescent (apoptotic) pathways. The Committee emphasizes topics that address the role of genes and pathways critical for myeloid development that have been implicated in the pathobiology of myeloid malignancies. Large scale genome resequencing efforts have identified most of the genes recurrently mutated in myeloid malignancies. Mechanistic studies of these mutated genes and pathways are expected to lead to a deeper understanding of leukemogenesis and potential therapeutic vulnerabilities. Additionally epigenomic, proteinomic, metabolomic, and bioinformatic methods are expected to be used routinely in the classification and prognosis and to guide therapy of myeloid malignancies. The major challenges for the next several years will be to integrate these with those from clinical, epidemiological, and conventional (morphologic, immunophenotypic, cytogenetic) laboratory data in order to provide treatment plans and to develop novel targeted therapies that offer the potential for more effective and less toxic treatments.
Clinical areas of interest
The Committee is interested in understanding the impact of each of the elements that contribute to disease development. The importance of germline genetic mutation in contributing risk alleles for development of myeloid malignancies is increasingly recognized. Genotyping patient disease samples to identify recurrent mutations associated with myeloid malignancies is becoming routine in clinical practice, leading to the possibility of precision medicine approaches with mutation-specific targeted therapies. The targeted management of the BCR-ABL-positive chronic myeloid leukemia (CML) is the paradigm for the treatment of myeloid malignancies, but numerous other targeted therapies for myeloid malignancies are in clinical development including kinase inhibitors, epigenomic inhibitors, spliceosome modulators, and others. Immunotherapy targeting myeloid malignancies is a rapidly growing investigational approach with a number of agents and strategies including monoclonal and multifunctional antibodies, cancer vaccines, modified T cells, including chimeric antigen receptors, and others. New effective drugs and therapeutic approaches will likely be developed for different types of myeloid malignancy targets. Defining drug and therapeutic efficacy and relevance for specific genotypes and/or disease subtypes using traditional Phase I, II, III studies or alternative methods are of clinical interest.
The Committee focuses on all aspects of research that have an impact on our understanding of the cellular mechanisms that lead to myeloid malignancies. Specific examples are:
- Use of genetically-engineered mouse models and/or CRISPR approaches to investigate the mechanisms by which new genes and mutations identified from next-generation sequencing contribute to leukemogenesis
- How we translate new scientific knowledge into clinical relevance
- New techniques that can be applied to the study of myeloid disorders: epigenetic, proteinomic, and metabolomic methodologies
Emerging areas of interest
Areas that are becoming increasingly important in the field of myeloid biology are:
- The role of the baseline genetic make-up of patients as providing risk alleles for myeloid leukemia development
- The role of genotyping using next-generation sequencing (NGS) will have in precision medicine approaches for the treatment of myeloid neoplasms
- How large amounts of data generated by NGS and other high-throughput technologies are integrated to produce new nosologic classification of myeloid malignancies and personalized (risk-adapted) therapies
- Mechanisms leading to progression of myeloid diseases to secondary acute myeloid leukemia
Potential overlap and resolution with other scientific committees
- Blood Disorders in Childhood: Because children develop myeloid malignancies, there is an inherent overlap with this committee. The issue of “age-oriented vs. “topic-oriented” can be resolved during the elaboration of annual topics.
- Hematopathology and Clinical Laboratory Hematology: Because the clinical diagnosis of myeloid disorders is made by hematopathologists, there is an inherent overlap with this committee.
- Hematopoiesis: Our Committee focuses on the malignant aspects of hematopoiesis and is inherently informed by an understanding of normal hematopoiesis. There is a natural bridge from the normal pathways to the malignant and, therefore, from this committee to ours.
- Myeloid Biology: Likewise for this committee, normal hematopoiesis informs an understanding of malignant processes.
- Bone Marrow Failure: Our Committee focuses on pathogenetic mechanisms, diagnosis and treatment of myeloid malignant hemopathies and has overlap with some bone marrow failure disorders, such as myelodysplastic syndromes.
- Immunology and Host Defense: The high impact of the biology of host defense and tolerance on tumor development and growth, as well immunotherapies are topics with potential overlap for our Committee.
Appropriate sessions at the ASH annual meeting
Our Committee would benefit from any presentation that addresses genes or pathways associated with the development, diagnosis, prognosis, and/or treatment of myeloid malignancies, both acute and chronic. Major advances in understanding of cellular events that are associated with myeloid malignancies or definition of new potential therapeutic targets would be areas of interest to this Committee.
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