Variant ALDH2 is associated with accelerated progression of bone marrow failure in Japanese Fanconi anemia patients

被引：140

作者：

Hira, Asuka ^{[1
]}

Yabe, Hiromasa ^{[2
]}

Yoshida, Kenichi ^{[3
]}

Okuno, Yusuke ^{[3
]}

Shiraishi, Yuichi ^{[4
]}

Chiba, Kenichi ^{[4
]}

Tanaka, Hiroko ^{[5
]}

Miyano, Satoru ^{[4
,5
]}

Nakamura, Jun ^{[6
]}

Kojima, Seiji ^{[7
]}

Ogawa, Seishi ^{[3
,8
]}

Matsuo, Keitaro ^{[9
]}

Takata, Minoru ^{[1
]}

Yabe, Miharu ^{[2
]}

机构：

[1] Kyoto Univ, Lab DNA Damage Signaling, Dept Late Effects Studies, Ctr Radiat Biol, Kyoto 6068501, Japan

[2] Tokai Univ, Sch Med, Dept Cell Transplantat & Regenerat Med, Isehara, Kanagawa 25911, Japan

[3] Univ Tokyo, Grad Sch Med, Canc Genom Project, Tokyo, Japan

[4] Univ Tokyo, Lab DNA Informat Anal, Tokyo, Japan

[5] Univ Tokyo, Lab Sequence Anal, Ctr Human Genome, Inst Med Sci, Tokyo, Japan

[6] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA

[7] Nagoya Univ, Grad Sch Med, Dept Pediat, Nagoya, Aichi 4648601, Japan

[8] Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto, Japan

[9] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan

来源：

BLOOD | 2013年 / 122卷 / 18期

关键词：

HEMATOPOIETIC STEM; MUTATIONS; GENE; CANCER; POLYMORPHISM; SENSITIVITY; DIAGNOSIS; ALDEHYDES; REGISTRY; SUBTYPE;

D O I：

10.1182/blood-2013-06-507962

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Fanconi anemia (FA) is a severe hereditary disorder with defective DNA damage response and repair. It is characterized by phenotypes including progressive bone marrow failure (BMF), developmental abnormalities, and increased occurrence of leukemia and cancer. Recent studies in mice have suggested that the FA proteins might counteract aldehyde-induced genotoxicity in hematopoietic stem cells. Nearly half of the Japanese population carries a dominant-negative allele (rs671) of the aldehyde-catalyzing enzyme ALDH2 (acetaldehyde dehydrogenase 2), providing an opportunity to test this hypothesis in humans. We examined 64 Japanese FA patients, and found that the ALDH2 variant is associated with accelerated progression of BMF, while birth weight or the number of physical abnormalities was not affected. Moreover, malformations at some specific anatomic locations were observed more frequently in ALDH2-deficient patients. Our current data indicate that the level of ALDH2 activity impacts pathogenesis in FA, suggesting the possibility of a novel therapeutic approach.

引用

页码：3206 / 3209

页数：4

共 26 条

[1]

AUERBACH AD, 1989, BLOOD, V73, P391

[2] Fanconi anemia and its diagnosis [J].