VEXAS syndrome: an adult-onset autoinflammatory disorder with underlying somatic mutation DOI
Ina Kötter, Martin Krusche

Current Opinion in Rheumatology, Journal Year: 2024, Volume and Issue: 37(1), P. 21 - 31

Published: Oct. 25, 2024

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) was first described in 2020, where a cohort of adults with unexplained fever or inflammation, systematic genetic testing performed and 25 men median age 64 years somatic mutations the UBA1 gene were identified. In current review, we aim to discuss relevant literature from January 2023 until July 2024 give new insights into pathophysiology, epidemiology, diagnosis treatment VEXAS.

Language: Английский

Hypomethylating agents for patients with VEXAS without myelodysplastic syndrome: Clinical outcome and longitudinal follow‐up of vacuolization and UBA1 clonal dynamics DOI Open Access
José Ramón Álamo Moreno,

Lucía Mont‐de Torres,

Sandra Castaño‐Díez

et al.

British Journal of Haematology, Journal Year: 2025, Volume and Issue: 206(2), P. 565 - 575

Published: Jan. 13, 2025

VEXAS syndrome is a haemato-inflammatory disease caused by somatic UBA1 mutations and characterized cytoplasmic vacuoles in myeloid erythroid precursor cells. Although there currently no standard treatment algorithm for VEXAS, patients are generally treated with anti-inflammatory therapies focused on symptom management, only partial effectiveness. Hypomethylating agents (HMA) have shown promise concomitant myelodysplastic (MDS), while the efficacy of HMA without MDS largely unknown. Furthermore, usefulness monitoring variant allele frequency (VAF) or vacuolization cells over course has not been extensively investigated. We evaluated four performed longitudinal analyses VAF during treatment. led to overall clinical improvement, dramatic reduction UBA1, normalization haematological inflammatory markers quantifiable decrease vacuolization, leading us speculate that unlike therapies, may well act as disease-modifying If these findings confirmed further studies, it could lead early use all patients-with MDS.

Language: Английский

Citations

1
Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine DOI Creative Commons
Roberto Pereira da Costa, Guilherme Sapinho, Matilde Bandeira

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 22, 2024

VEXAS syndrome is a recently described autoinflammatory caused by the somatic acquisition of UBA1 mutations in myeloid precursors and frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying diagnosis. We describe case atypical resembling late-onset axial spondylarthritis, later progressing to systemic inflammatory chondritis, cutaneous vasculitis, transfusion-dependent anemia, requiring high doses steroids. Ruxolitinib was used as first steroid-sparing strategy without response. However, azacitidine showed activity controlling both inflammation mutant clone. This raises question whether azacitidine’s anti-inflammatory effects are dependent on or independent clonal control. discuss potential relevance molecular remission highlight importance multidisciplinary team for care such complex patients.

Language: Английский

Citations

4
VEXAS, Chediak–Higashi syndrome and Danon disease: myeloid cell endo-lysosomal pathway dysfunction as a common denominator? DOI Creative Commons

Coline Savy,

Maxence Bourgoin,

Thomas Cluzeau

et al.

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 26, 2025

Abstract Vacuolization of hematopoietic precursors cells is a common future several otherwise non-related clinical settings such as VEXAS, Chediak–Higashi syndrome and Danon disease. Although these disorders have priori nothing to do with one other from point view, all share abnormal vacuolization in different cell types including the erythroid/myeloid lineage that likely consequence moderate drastic dysfunctions ubiquitin proteasome system and/or endo-lysosomal pathway. Indeed, genes affected three diseases UBA1, LYST or LAMP2 are known be direct indirect regulators lysosome trafficking function modes autophagy. Furthermore, highly expressed more mature myeloid pointing out their important cells. deficiency for instance associated alterations architecture function. It thus well established disease patients harbor invalidating mutations exhibit giant lysosomes containing undigested materials characteristic defects fusion autophagosomes, feature also found VEXAS CHS. Other similarities regarding include granulocyte monocyte recurrent inflammatory climate. In present review we discuss possibility some manifestations diseases, notably ones consecutive dysfunction pathway myeloid/erythroid progenitors neutrophiles, monocytes macrophages. Finally, propose reacidification way reinducing functionalities autophagy potential approach better management diseases.

Language: Английский

Citations

0
Myeloid neoplasm inspired intensive therapy in VEXAS syndrome: A single‐centre experience DOI Creative Commons
Maël Heiblig, Adriana Pleşa,

Juliet Tantot

et al.

British Journal of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Summary There is still no standard of care and unmet medical needs in refractory/advanced VEXAS (vacuoles myeloid progenitors, E1 ubiquitin activating enzyme, X‐linked, autoinflammatory manifestations somatic) syndrome with or without associated haematological neoplasm. We report the clinical outcome four multirefractory/advanced patients treated acute leukaemia‐like therapeutic approaches. All responded to inflammatory/haematological VEXAS‐related features, which were measurable residual disease response (partial complete). Prospective studies evaluating new effective strategies order reduce clonal burden are warranted.

Language: Английский

Citations

0
VEXAS syndrome: A newly identified X-Linked hematoinflammatory disorder – A comprehensive overview of its genetic, molecular, inflammatory, and clinical landscape DOI
Alpana Singh, Rishabh Chaudhary

Journal of Autoimmunity, Journal Year: 2025, Volume and Issue: 154, P. 103425 - 103425

Published: April 29, 2025

Language: Английский

Citations

0
Assessing the efficacy of allogeneic hematopoietic cell transplantation in VEXAS syndrome: results of a systematic review and meta-analysis DOI
Razan Mohty, Tea Reljic,

Nayef Abdel-Razeq

et al.

Bone Marrow Transplantation, Journal Year: 2024, Volume and Issue: 59(10), P. 1423 - 1427

Published: July 26, 2024

Language: Английский

Citations

2
VEXAS Syndrome: A Comprehensive Review of Current Therapeutic Strategies and Emerging Treatments DOI Open Access
Safi Alqatari,

Abdulaziz A. Alqunais,

Shahad Mufeed Alali

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(22), P. 6970 - 6970

Published: Nov. 19, 2024

VEXAS syndrome is a recently identified autoinflammatory disorder resulting from somatic mutations in the UBA1 gene, leading to complex spectrum of severe inflammatory and hematologic manifestations. The absence established treatment guidelines variability clinical presentation make its management particularly challenging. Current therapeutic approaches are often based on limited evidence, their effectiveness remains inconsistent. This review seeks consolidate existing knowledge strategies for syndrome, offering critical evaluation efficacy addressing gaps current literature. As recognition grows, there an urgent need explore more targeted, effective treatments that can address both aspects disease. By providing comprehensive analysis landscape, this aims guide clinicians researchers toward developing effective, long-term life-threatening condition.

Language: Английский

Citations

2
Clonal cytopenia of undetermined significance: definitions, risk and therapeutic targets DOI Creative Commons

Cristian C. Taborda,

Amer M. Zeidan,

Lourdes M. Mendez

et al.

Frontiers in Hematology, Journal Year: 2024, Volume and Issue: 3

Published: July 12, 2024

Cancer-related somatic genetic alterations are detectable in the blood of individuals without hematologic malignancy, reflecting outgrowth a mutated stem/progenitor cell population, phenomenon termed clonal hematopoiesis (CH). When accompanied by an unexplained cytopenia(s), CH is further refined to cytopenia undetermined significance (CCUS) whereas, finding mutation/alteration setting normal complement counts called indeterminate potential (CHIP). CHIP and CCUS now recognized precursor conditions myeloid neoplasms. Advances understanding epidemiology metrics associated with evolution malignancy has permitted elaboration risk stratification tools poised for use clinic initial clinical investigations seeking disrupt natural history high CCUS. In this review, we focus on current its classification, therapeutic targets

Language: Английский

Citations

1
Rapid growth of acquired UBA1 mutations predisposes male patients to low-risk MDS DOI Creative Commons
Peng Li,

Alnoor Fnu,

Wei Xie

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 23, 2024

Abstract VEXAS (vacuoles, E1-ubiquitin-like modifier activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory disorder caused by acquired UBA1 mutations in hematopoietic precursor cells. The prevalence, clinical significance, and genomic landscape of UBA1variants patients with hematologic malignancies (HM) remains unexplored. We analyzed the profiles 86 carrying 17 different amongst an unbiased cohort 8,976 HM patients. Specific genetic features seen more frequently pathogenic variants (PV) versus those uncertain significance (VUS) included: marked male predominance (98% 80%, P=0.002), macrocytic anemia (MCV 105 ± 1.4 fl 96 fl, p=0.01), frequent dominant clones without concurrent somatic (53% 15%, p=0.004), association molecularly distinct low-risk myelodysplastic (MDS; 13%) superior overall survival (OS). Interestingly, while PV resemble clonal cytopenia unknown (CCUS), rapid expansion predispose to convert low-grade MDS notably hastened progression compared wild-type CCUS. This “clone surge stability” (CS) mechanism that emphasizes unique pathobiology UBA1mutations supports it as entity.

Language: Английский

Citations

0
Role of allogeneic hematopoietic cell transplantation in VEXAS syndrome DOI Creative Commons

Ajoy L. Dias,

Emma M. Groarke, Dennis D. Hickstein

et al.

Annals of Hematology, Journal Year: 2024, Volume and Issue: 103(11), P. 4427 - 4436

Published: Aug. 22, 2024

Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly diagnosed syndrome comprising severe systemic inflammatory and hematological manifestations including myelodysplastic plasma cell dyscrasia. Since its discovery four years ago, several groups have identified pleomorphic clinical phenotypes, but few effective medical therapies exist which include Janus Kinase (JAK) inhibitors, interleukin inhibitors (IL-1 IL-6), hypomethylating agents. Prospective trials are lacking at this time most patients remain corticosteroid dependent. has high morbidity from frequent life threatening symptoms risk of progression to malignancies an overall survival 50% 10 years. Allogeneic stem transplant (allo-HCT) curative option for disease caused by somatic mutations in the UBA1 gene. Here we outline role allo-HCT treating with syndrome, highlighting outcomes single-institution studies case reports. will be required precisely define management syndrome.

Language: Английский

Citations

0