Familial CEBPA-mutated acute myeloid leukemia |
| |
| Affiliation: | 1. Centre for Haemato-Oncology, Barts Cancer Institute, London, United Kingdom;2. Laboratory of Hematology, Biology and Pathology Center, Centre Hospitalier Régional Universitaire (CHRU) of Lille, Lille, France;1. Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, and Harvard Stem Cell Institute, Boston, MA;2. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA;1. Translational Hematology and Oncology Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA;2. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA;3. Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia;4. Medizinische Klinik V, Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Germany;1. Department of Pharmaceutical Sciences, St Jude Children''s Research Hospital, Memphis, TN, USA;2. Department of Oncology, St Jude Children''s Research Hospital, Memphis, TN, USA;3. Department of Computational Biology, St Jude Children''s Research Hospital, Memphis, TN, USA;4. Department of Biostatistics, St Jude Children''s Research Hospital, Memphis, TN, USA;5. Department of Pathology, St Jude Children''s Research Hospital, Memphis, TN, USA;6. Hematological Malignancies Program, Comprehensive Cancer Center, St Jude Children''s Research Hospital, Memphis, TN, USA;7. Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan;8. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan;9. Department of Biostatistics, College of Medicine, Public Health and Health Professions, University of Florida, Gainesville, FL, USA;10. Department of Pathology and Laboratory Medicine, Nationwide Children''s Hospital, and Departments of Pathology and Pediatrics, Ohio State University, Columbus, OH, USA;12. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA;13. Maine Children''s Cancer Program, Scarborough, ME, USA;14. Department of Pediatrics, Duke University, Durham, NC, USA;15. Cook Children''s Medical Center, Fort Worth, TX, USA;p. Pediatric Hematology Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA;q. Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China;r. McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA;s. Department of Pediatrics and Center for Childhood Cancer Research, Children''s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;t. Department of Pediatrics, Benioff Children''s Hospital and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA;1. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;2. Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, TX;3. Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX;4. Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX;9. Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX;5. Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD;6. Center for Human Immunobiology, Texas Children''s Hospital, Baylor College of Medicine, Houston, TX;8. Department of Pediatrics, Texas Children''s Cancer & Hematology Center, Baylor College of Medicine, Houston, TX;7. Section of Hematology/Oncology, Department of Medicine, Comprehensive Cancer Research Center, University of Chicago, Chicago, IL |
| |
| Abstract: | Familial CEBPA-mutated acute myeloid leukemia (AML) represents a recognized leukemia predisposition syndrome, with several families described in the literature since the initial report in 2004. The pathological features and long-term survival of individuals with familial CEBPA-mutated AML are reminiscent of sporadic CEBPAdm AML. Germline mutations predominantly localize to the N-terminal and are associated with near complete penetrance, with age of AML onset from 2–50 years, frequently accompanied by the acquisition of a second CEBPA mutation in C-terminal domain. Patients appear to have a significant risk of late AML recurrence and these typically represent independent leukemic episodes, characterized by a unique molecular profile that is distinct from that of the preceding tumor. While these patients respond well to salvage therapies, allogeneic hematopoietic stem cell transplantation (HSCT) should be considered for patients with high-risk features at presentation or recurrent disease, with the aim of eradicating the germline mutation and improving long-term survival. In contrast, inherited C-terminal CEBPA mutations occur less frequently and appear to demonstrate reduced penetrance, impeding clinical detection and surveillance. |
| |
| Keywords: | Familial CEBPA Acute myeloid leukemia Germline Mutation |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
