Somatic Mutations and Clonal Hematopoiesis in Aplastic Anemia

• Published in: The New England journal of medicine Vol. 373; no. 1; pp. 35 - 47
• Main Authors: Yoshizato, Tetsuichi, Dumitriu, Bogdan, Hosokawa, Kohei, Makishima, Hideki, Yoshida, Kenichi, Townsley, Danielle, Sato-Otsubo, Aiko, Sato, Yusuke, Liu, Delong, Suzuki, Hiromichi, Wu, Colin O, Shiraishi, Yuichi, Clemente, Michael J, Kataoka, Keisuke, Shiozawa, Yusuke, Okuno, Yusuke, Chiba, Kenichi, Tanaka, Hiroko, Nagata, Yasunobu, Katagiri, Takamasa, Kon, Ayana, Sanada, Masashi, Scheinberg, Phillip, Miyano, Satoru, Maciejewski, Jaroslaw P, Nakao, Shinji, Young, Neal S, Ogawa, Seishi
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 02.07.2015
• Subjects: Acute myeloid leukemia; Age; Age Factors; Aged; Anemia; Anemia, Aplastic - blood; Anemia, Aplastic - genetics; Anemia, Aplastic - mortality; Aplastic anemia; Bone marrow; Cancer; Clone Cells; Erythrocytes; Female; Gene frequency; Hematopoiesis - genetics; Humans; Immune system; Immunosuppressive agents; Karyotyping; Leukemia, Myeloid, Acute - genetics; Male; Middle Aged; Mutation; Myelodysplastic syndrome; Myelodysplastic Syndromes - genetics; Myeloid leukemia; Pancytopenia; Polymorphism, Single Nucleotide; Risk Factors; Sequence Analysis, DNA; Cleveland Ohio; United States > US; Japan
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1414799

Although aplastic anemia is responsive to immunosuppressive therapy, small subpopulations of hematopoietic cells with clonal gene mutations may exist, and different sets of mutations show distinct clinical behavior and response to therapy. Acquired aplastic anemia is caused by immune-mediated destruction of hematopoietic stem and progenitor cells. 1 CD34+ cells and early progenitors are uniformly reduced in aplastic anemia. 2 Bone marrow transplantation is curative, and patients may also have a response to immunosuppressive therapy. 3 , 4 With improved survival, the late development of myelodysplastic syndromes, acute myeloid leukemia (AML), or both has been noted in about 15% of patients and termed “clonal evolution.” 5 Although “clonal evolution” historically has been used to describe the development of cancer in patients with an immune disease, this term is a misnomer, since there is evidence of clonal hematopoiesis associated . . .