Clonal Hematopoiesis in a Broad Age Spectrum of Systemic Vasculitis

Gutierrez-Rodrigues, Fernanda; Jones, Alexander; Wells, Kristina; Hironaka, Dalton; Rankin, Cameron; Sikora, Keith A.; Quinn, Kaitlin A.; Ferrada, Marcela; Patel, Bhavisha; Grayson, Peter C.; Young, Neal

doi:10.1182/blood-2022-160327

Cited by 9 publications

(26 citation statements)

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“…Cytogenic analysis of bone marrow cells has shown normal karyotype in the majority (80%) of patients with VEXAS and no cases of complex karyotypes have been reported. 45 Cytogenic aberrations, when present have included del(7q), del(11q), del(13q), del(20q), and -Y. 45 Additional clonal hematopoietic mutations, most commonly DNMT3A and TET2, have been reported in a large French cohort with frequencies of observance near 25% of patients with VEXAS.…”

Section: Bone Marrowmentioning

confidence: 99%

“…45 Cytogenic aberrations, when present have included del(7q), del(11q), del(13q), del(20q), and -Y. 45 Additional clonal hematopoietic mutations, most commonly DNMT3A and TET2, have been reported in a large French cohort with frequencies of observance near 25% of patients with VEXAS. 16 In our experience, additional somatic mutations nears 50% and the presence of either DNMT3A or TET2 is associated with increased risk of mortality.…”

Section: Bone Marrowmentioning

confidence: 99%

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VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

Koster,

Lasho,

Olteanu

et al. 2023

American J Hematol

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VEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non‐specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin‐6 inhibitors and JAK–STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.

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Section: Bone Marrowmentioning

confidence: 99%

Section: Bone Marrowmentioning

confidence: 99%

VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

Koster,

Lasho,

Olteanu

et al. 2023

American J Hematol

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“…Individuals with UBA1 mutation also sometimes display additional mutations, for instance in the DNMT3A and TET2 genes. 11,12…”

Section: Pathophysiologymentioning

confidence: 99%

“…The functional consequences of these mutations are not fully understood at this point in time. Individuals with UBA1 mutation also sometimes display additional mutations, for instance in the DNMT3A and TET2 genes 11,12 …”

Section: Pathophysiologymentioning

confidence: 99%

VEXAS‐Syndrome, a newly described autoinflammatory systemic disease with dermatologic manifestations

Baur,

Stoevesandt,

Hueber

et al. 2023

J Deutsche Derma Gesell

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SummaryVEXAS syndrome is a recently identified autoinflammatory systemic disease caused by an acquired somatic mutation of the X‐linked UBA1 gene, the key enzyme of the first step of ubiquitylation. The acronym VEXAS stands for the characteristics Vacuoles, E1 enzyme, X‐linked, autoinflammatory and somatic. The disease occurs in advanced adulthood preferentially in men and is characterized by hematological, rheumatological and dermatological symptoms. The latter include neutrophil‐rich lesions reminiscent of Sweet's syndrome, erythema nodosum‐ and panniculitis‐like skin manifestations and recurrent polychondritis of the nose and auricles. The presence of cytoplasmic vacuoles in myeloid and erythroid precursors in the bone marrow is characteristic. In up to half of the cases, VEXAS syndrome is associated with myelodysplastic syndrome. Dermatologists should be familiar with the clinical picture, as skin symptoms are often the first indicator of the disease. Molecular diagnostics are essential for confirming the diagnosis and risk stratification of affected patients. In this minireview we provide an overview of the pathophysiology, diagnosis and therapy of VEXAS syndrome and illustrate its clinical picture with two own cases.

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“…Jüngst wurden weitere pathogene, somatische Mutationen im UBA1 ‐Gen beschrieben, unter anderem c.167C>T im Kodon 56, c.1861A > T im Kodon 621 sowie Splice‐Varianten (c.118‐1G > C und c.118‐2A > G), 4,8,9,10 deren funktionelle Auswirkungen noch nicht vollumfänglich verstanden sind. Individuen mit UBA1 ‐Mutation zeigen zudem mitunter weitere Mutationen, beispielsweise in den DNMT3A ‐ und TET2 ‐Genen 11,12 …”

Section: Pathophysiologieunclassified

VEXAS‐Syndrom, eine neu beschriebene autoinflammatorische Systemerkrankung mit dermatologischen Manifestationen

Baur,

Stoevesandt,

Hueber

et al. 2023

J Deutsche Derma Gesell

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ZusammenfassungDas VEXAS‐Syndrom ist eine kürzlich erstbeschriebene autoinflammatorische Systemerkrankung, die auf einer erworbenen, somatischen Mutation des X‐chromosomal lokalisierten UBA1‐Gens, dem Schlüsselenzym des ersten Schritts der Ubiquitinierung, beruht. Das Akronym VEXAS steht für die Charakteristika Vacuoles, E1 enzyme, X‐linked, autoinflammatory und somatic. Die Erkrankung tritt im fortgeschrittenen Erwachsenenalter vorzugsweise bei Männern auf und ist insbesondere durch hämatologische, rheumatologische und dermatologische Symptome gekennzeichnet. Letztere umfassen unter anderem neutrophilenreiche, an das Sweet‐Syndrom erinnernde Läsionen, Erythema nodosum‐ und Pannikulitis‐artige Hauterscheinungen sowie rezidivierende Polychondritiden an Nase und Ohrmuscheln. Das Vorliegen zytoplasmatischer Vakuolen in myeloiden und erythroiden Vorläuferzellen des Knochenmarks ist charakteristisch. In bis zur Hälfte der Fälle ist das VEXAS‐Syndrom mit einem myelodysplastischen Syndrom vergesellschaftet. Dermatologen sollten das Krankheitsbild kennen, da Hauterscheinungen oft der erste Indikator für die Erkrankung sind. Eine molekulare Diagnostik ist essenziell für die Diagnosesicherung und die Risikostratifizierung betroffener Patienten. In dieser Arbeit geben wir einen Überblick über die Pathophysiologie, Diagnostik und Therapie des VEXAS‐Syndroms und illustrieren das klinische Spektrum anhand zweier eigener Fälle.

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Clonal Hematopoiesis in a Broad Age Spectrum of Systemic Vasculitis

Cited by 9 publications

References 0 publications

VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

VEXAS‐Syndrome, a newly described autoinflammatory systemic disease with dermatologic manifestations

VEXAS‐Syndrom, eine neu beschriebene autoinflammatorische Systemerkrankung mit dermatologischen Manifestationen

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