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Spectrum of Genetic Alterations in Acquired Aplastic Anemia

Original Publication Date: 
Monday, February 10, 2014

Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.

Abstract # 2464

Tetsuichi Yoshizato, M.D., Bogdan Dumitriu, M.D., Kohei Hosokawa, M.D., Ph.D., Hideki Makishima, M.D., Ph.D., Kenichi Yoshida, M.D., Yusuke Okuno, Kenichi Chiba, Hiroko Tanaka, Yuichi Shiraishi, Ph.D., Yasunobu Nagata, M.D., Takamasa Katagiri, Ph.D., Ayana Kon, M.D., Michael J. Clemente, Masashi Sanada, M.D., Satoru Miyano, Ph.D.,, Jaroslaw P. Maciejewski, M.D., Ph.D., Shinji Nakao, M.D., Ph.D., Neal S. Young, M.D., and Seishi Ogawa, M.D., Ph.D.

Acquired aplastic anemia (resulting from exposure to certain environmental factors) is caused by the destruction of hematopoietic stem cells, which make blood cells in the bone marrow. Some patients with acquired aplastic anemia develop genetic mutations, or changes in their genes after birth, that result in progression of their aplastic anemia to paroxysmal nocturnal hemoglobinuria, myelodysplastic syndromes (MDS), or acute myelogenous leukemia (AML). The relationships between these diseases suggest that they share a common origin.

The goal of this study was to identify the genes that play a role in the formation of abnormal blood cells in acquired aplastic anemia. The researchers tested DNA from the blood of 192 Japanese patients and 86 American patients with aplastic anemia for mutations in 51 genes. About 40% of the Japanese group had severe or very severe aplastic anemia but had responded well to immunosuppressive treatment (to suppress their immune system). All of the American patients had severe or very severe aplastic anemia and all had undergone immunosuppressive treatment. About 65% of these patients had responded to the therapy.

Key findings:

  • The most common mutations in the Japanese patients were in the DNMT3A (3.6% of patients), ZRSR2 (3%), ASXL1 (2.6%), and BCOR (2.0%) genes.
  • The most common mutations in the American patients were in the BCOR (13.8% of patients), DNMT3A (11.5%), ASXL1 (10.3%), PIGA (6.9%), and CSM.D.1 (4.6%) genes.
  • In both groups, mutations were more common in older patients and those with a better response to immunosuppressive treatment.
  • Approximately one-third of American patients with mutations and one-fifth of those without mutations developed MDS or AML


  • Mutations in genes that are commonly involved in bone marrow failure syndromes can drive the development of abnormal bone marrow cells in aplastic anemia.
  • The study did not find a correlation between genetic mutations and progression of acquired aplastic anemia to MDS or AML.
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