Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1.

Autor: Obiorah IE; Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute.; Hematology Section, Department of Laboratory Medicine, Clinical Center., Patel BA; Hematology Branch, National Heart, Lung, and Blood Institute., Groarke EM; Hematology Branch, National Heart, Lung, and Blood Institute., Wang W; Hematology Section, Department of Laboratory Medicine, Clinical Center., Trick M; Hematology Section, Department of Laboratory Medicine, Clinical Center., Ombrello AK; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Ferrada MA; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD., Wu Z; Hematology Branch, National Heart, Lung, and Blood Institute., Gutierrez-Rodrigues F; Hematology Branch, National Heart, Lung, and Blood Institute., Lotter J; Hematology Branch, National Heart, Lung, and Blood Institute., Wilson L; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Hoffmann P; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Cardona DO; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Patel N; Hematology Section, Department of Laboratory Medicine, Clinical Center., Dulau-Florea A; Hematology Section, Department of Laboratory Medicine, Clinical Center., Kastner DL; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Grayson PC; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD., Beck DB; Metabolic, Cardiovascular, and Inflammatory Disease Genomics Branch, National Human Genome Research Institute, and., Young NS; Hematology Branch, National Heart, Lung, and Blood Institute., Calvo KR; Hematology Section, Department of Laboratory Medicine, Clinical Center.
Jazyk: angličtina
Zdroj: Blood advances [Blood Adv] 2021 Aug 24; Vol. 5 (16), pp. 3203-3215.
DOI: 10.1182/bloodadvances.2021004976
Abstrakt: Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.
(© 2021 by The American Society of Hematology.)
Databáze: MEDLINE