Gene Mutations in Aplastic Anemia | Aplastic Anemia and MDS International Foundation

Gene Mutations in Aplastic Anemia

Original Publication Date: 
Monday, January 12, 2015

Note: This review is based upon a presentation at the 2014 American Society of Hematology (ASH) Annual Meeting, December 6 - 9 in San Francisco, CA.The full abstract may be reviewed on the ASH Annual Meeting Web site

Tetsuichi Yoshizato, M.D.; Bogdan Dumitriu, M.D.; Kohei Hosokawa, M.D., Ph.D.; Hideki Makishima, M.D., Ph.D.; Kenichi Yoshida, M.D., Ph.D.; Aiko Sato, Ph.D.; Yusuke Okuno, M.D., Ph.D.; Keisuke Kataoka, M.D., Ph.D.; Kenichi Chiba, Ph.D.; Hiroko Tanaka, Yuichi Shiraishi, Ph.D.; Yasunobu Nagata, M.D., Ph.D.; Hiromichi Suzuki, M.D.; Yusuke Sato, M.D.; Yusuke Shiozawa, M.D.; Takamasa Katagiri, Ph.D.; Ayana Kon, M.D.; Michael Clemente, MS, Masashi Sanada, M.D., Ph.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.

 

Abstract 253: Chronological Analysis of Clonal Evolution in Acquired Aplastic Anemia

Acquired (non-inherited) aplastic anemia apparently results from the immune system’s destruction of the bone marrow cells that form blood cells. Up to half of patients with aplastic anemia have abnormal clones, or copies, of the cells that form blood cells in the bone marrow. These clones are signs of paroxysmal nocturnal hemoglobinuria, another bone marrow failure disease. About 10 to 15% of patients with aplastic anemia develop MDS or acute myelogenous leukemia (AML).

The authors analyzed DNA from 439 patients with aplastic anemia from the United States and Japan with a focus on 103 genes that are often mutated in bone marrow cancers. When possible, the researchers determined when the mutations happened.

Key findings:

  • About one third of patients had mutations in genes that are commonly affected in bone marrow cancers. About a third of these patients had several different mutations.
  • Mutations in aplastic anemia typically involved the PIGA, BCOR or BCORL1, DNMT3A, and ASXL1 genes.
  • Older patients were more likely to have acquired mutations. But these mutations did not affect their likelihood of responding to treatment to suppress their immune system or their survival.
  • Patients with mutations in both PIGA and BCOR or BCORL1 tended to survive longer. Seventeen other mutations were associated with shorter survival.
  • Patients’ bone marrow often formed abnormal clones gradually. The pace of clone development had no effect on blood counts or development of abnormal chromosomes, abnormal cells in the bone marrow, or leukemia.
  • Patients formed abnormal clones before they developed MDS or leukemia, and the clones could often be detected at the time of diagnosis.   

Conclusion:

  • Gene mutations could be used to more accurately predict outcomes in patients with aplastic anemia.
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