Red cells, iron, and erythropoiesis: Telomere attrition and candidate gene mutations preceding monosomy 7 in aplastic anemia

Bogdan Dumitriu, Xingmin Feng, Danielle M. Townsley, Yasutaka Ueda, Tetsuichi Yoshizato, Rodrigo T. Calado, Yanqin Yang, Yoshiyuki Wakabayashi, Sachiko Kajigaya, Seishi Ogawa, Jun Zhu, Neal S. Young

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The pathophysiology of severe aplastic anemia (SAA) is immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs). Most patients respond to immunosuppressive therapies, but a minority transform to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), frequently associated with monosomy 7 (-7). Thirteen SAA patients were analyzed for acquired mutations in myeloid cells at the time of evolution to 27, and all had a dominant HSPC clone bearing specific acquired mutations. However, mutations in genes associated with MDS/AML were present in only 4 cases. Patients who evolved to MDS and AML showed marked progressive telomere attrition before the emergence of 27. Single telomere length analysis confirmed accumulation of short telomere fragments of individual chromosomes. Our results indicate that accelerated telomere attrition in the setting of a decreased HSPC pool is characteristic of early myeloid oncogenesis, specifically chromosome 7 loss, in MDS/AML after SAA, and provides a possible mechanism for development of aneuploidy.

Original languageEnglish
Pages (from-to)706-709
Number of pages4
JournalBlood
Volume125
Issue number4
DOIs
StatePublished - 22 Jan 2015
Externally publishedYes

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