Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)

Jan Philipp Bewersdorf; Zhuoer Xie; Rafael Bejar; Uma Borate; Jacqueline Boultwood; Andrew M Brunner; Rena Buckstein; Hetty E Carraway; Jane E Churpek; Naval G Daver; Matteo Giovanni Della Porta; Amy E DeZern; Pierre Fenaux; Maria E Figueroa; Steven D Gore; Elizabeth A Griffiths; Stephanie Halene; Robert P Hasserjian; Christopher S Hourigan; Tae Kon Kim; Rami Komrokji; Vijay K Kuchroo; Alan F List; Sanam Loghavi; Ravindra Majeti; Olatoyosi Odenike; Mrinal M Patnaik; Uwe Platzbecker; Gail J Roboz; David A Sallman; Valeria Santini; Guillermo Sanz; Mikkael A Sekeres; Maximilian Stahl; Daniel T Starczynowski; David P Steensma; Justin Taylor; Omar Abdel-Wahab; Mina L Xu; Michael R Savona; Andrew H Wei; Amer M Zeidan

doi:10.1016/j.blre.2023.101072

Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1^st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)

Blood Rev. 2023 Jul:60:101072. doi: 10.1016/j.blre.2023.101072. Epub 2023 Mar 11.

Authors

Jan Philipp Bewersdorf¹, Zhuoer Xie², Rafael Bejar³, Uma Borate⁴, Jacqueline Boultwood⁵, Andrew M Brunner⁶, Rena Buckstein⁷, Hetty E Carraway⁸, Jane E Churpek⁹, Naval G Daver¹⁰, Matteo Giovanni Della Porta¹¹, Amy E DeZern¹², Pierre Fenaux¹³, Maria E Figueroa¹⁴, Steven D Gore¹⁵, Elizabeth A Griffiths¹⁶, Stephanie Halene¹⁷, Robert P Hasserjian¹⁸, Christopher S Hourigan¹⁹, Tae Kon Kim²⁰, Rami Komrokji², Vijay K Kuchroo²¹, Alan F List²², Sanam Loghavi²³, Ravindra Majeti²⁴, Olatoyosi Odenike²⁵, Mrinal M Patnaik²⁶, Uwe Platzbecker²⁷, Gail J Roboz²⁸, David A Sallman², Valeria Santini²⁹, Guillermo Sanz³⁰, Mikkael A Sekeres¹⁴, Maximilian Stahl³¹, Daniel T Starczynowski³², David P Steensma³³, Justin Taylor¹⁴, Omar Abdel-Wahab¹, Mina L Xu³⁴, Michael R Savona²⁰, Andrew H Wei³⁵, Amer M Zeidan³⁶

Affiliations

¹ Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
² Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
³ Division of Hematology and Oncology, Moores Cancer Center, UC San Diego, La Jolla, CA, USA.
⁴ Ohio State University Comprehensive Cancer/ James Cancer Hospital, Ohio State University, Columbus, OH, USA.
⁵ Blood Cancer UK Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁶ Leukemia Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁷ Department of Medical Oncology/Hematology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Leukemia Program, Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Department of Hematology, Oncology, and Palliative Care, Carbone Cancer Center, The University of Wisconsin-Madison, Madison, WI, USA.
¹⁰ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ IRCCS Humanitas Clinical and Research Center & Humanitas University, Department of Biomedical Sciences, via Manzoni 56, 20089 Rozzano - Milan, Italy.
¹² Division of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA.
¹³ Hôpital Saint Louis, Assistance Publique Hôpitaux de Paris and Paris Cité University, Paris, France.
¹⁴ Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
¹⁵ National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD, USA.
¹⁶ Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
¹⁷ Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA.
¹⁸ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
¹⁹ Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, and Myeloid Malignancies Program, National Institutes of Health, Bethesda, MD, USA.
²⁰ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Evergrande Center for Immunologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
²² Precision BioSciences, Inc., Durham, NC, USA.
²³ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²⁴ Division of Hematology, Department of Medicine, Cancer Institute, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
²⁵ Leukemia Program, University of Chicago Medicine and University of Chicago Comprehensive Cancer Center, Chicago, IL, USA.
²⁶ Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
²⁷ Leipzig University Hospital, Leipzig, Germany.
²⁸ Weill Cornell Medical College, New York, NY, USA.
²⁹ MDS Unit, Hematology, AOUC, University of Florence, Italy.
³⁰ Health Research Institute La Fe, Valencia, Spain; Hospital Universitario y Politécnico La Fe, Valencia, Spain; CIBERONC, IS Carlos III, Madrid, Spain.
³¹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
³² Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
³³ Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
³⁴ Departments of Pathology & Laboratory Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA.
³⁵ Department of Haematology, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research and University of Melbourne, Victoria, Australia.
³⁶ Section of Hematology, Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA. Electronic address: amer.zeidan@yale.edu.

PMID: 36934059
DOI: 10.1016/j.blre.2023.101072

Abstract

Biological events that contribute to the pathogenesis of myelodysplastic syndromes/neoplasms (MDS) are becoming increasingly characterized and are being translated into rationally designed therapeutic strategies. Herein, we provide updates from the first International Workshop on MDS (iwMDS) of the International Consortium for MDS (icMDS) detailing recent advances in understanding the genetic landscape of MDS, including germline predisposition, epigenetic and immune dysregulation, the complexities of clonal hematopoiesis progression to MDS, as well as novel animal models of the disease. Connected to this progress is the development of novel therapies targeting specific molecular alterations, the innate immune system, and immune checkpoint inhibitors. While some of these agents have entered clinical trials (e.g., splicing modulators, IRAK1/4 inhibitors, anti-CD47 and anti-TIM3 antibodies, and cellular therapies), none have been approved for MDS. Additional preclinical and clinical work is needed to develop a truly individualized approach to the care of MDS patients.

Keywords: Animal models; Genetics; Immunology; MDS; Myelodysplastic syndrome; Novel therapies.

Publication types

Review
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell- and Tissue-Based Therapy
Epigenomics
Humans
Myelodysplastic Syndromes* / etiology
Myelodysplastic Syndromes* / therapy
Neoplasms*
Protein Processing, Post-Translational