Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome.

Apr 17, 2023

Experts: Hiroyoshi Kunimoto,Ayaka Miura,Ayaka Maeda,Naomi Tsuchida,Yuri Uchiyama,Yosuke Kunishita,Yuki Nakajima,Kaoru Takase-Minegishi,Ryusuke Yoshimi,Takuya Miyazaki,Maki Hagihara,Etsuko Yamazaki,Yohei Kirino,Naomichi Matsumoto,Hideaki Nakajima

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a new disease entity with autoinflammatory disorders (AID) driven by somatic variants in UBA1 that frequently co-exists with myelodysplastic syndromes (MDS). Clinicopathological and molecular features of Japanese cases with VEXAS-associated MDS remain elusive. We previously reported high prevalence of UBA1 variants in Japanese patients with relapsing polychondritis, in which 5 cases co-occurred with MDS. Here, we report clinicopathological and variant profiles of these 5 cases and 2 additional cases of MDS associated with VEXAS syndrome. Clinical characteristics of these cases included high prevalence of macrocytic anemia with marked cytoplasmic vacuoles in myeloid/erythroid precursors and low bone marrow (BM) blast percentages. All cases were classified as low or very low risk by the revised international prognostic scoring system (IPSS-R). Notably, 4 out of 7 cases showed significant improvement of anemia by treatment with prednisolone (PSL) or cyclosporin A (CsA), suggesting that an underlying inflammatory milieu induced by VEXAS syndrome may aggravate macrocytic anemia in VEXAS-associated MDS. Targeted deep sequencing of blood samples suggested that MDS associated with VEXAS syndrome tends to involve a smaller number of genes and lower risk genetic lesions than classical MDS.
© 2023. Japanese Society of Hematology.

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ABOUT THE EXPERTS

Hiroyoshi Kunimoto,Ayaka Miura,Ayaka Maeda,Naomi Tsuchida,Yuri Uchiyama,Yosuke Kunishita,Yuki Nakajima,Kaoru Takase-Minegishi,Ryusuke Yoshimi,Takuya Miyazaki,Maki Hagihara,Etsuko Yamazaki,Yohei Kirino,Naomichi Matsumoto,Hideaki Nakajima

Hiroyoshi Kunimoto

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Ayaka Miura

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Ayaka Maeda

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Naomi Tsuchida

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.

Yuri Uchiyama

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.

Yosuke Kunishita

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Yuki Nakajima

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Kaoru Takase-Minegishi

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Ryusuke Yoshimi

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Takuya Miyazaki

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Maki Hagihara

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Etsuko Yamazaki

Clinical Laboratory Department, Yokohama City University Hospital, Yokohama, Japan.

Yohei Kirino

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.

Naomichi Matsumoto

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Hideaki Nakajima

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan. hnakajim@yokohama-cu.ac.jp.