Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome.

Abstract

In a patient with refractory anemia with excess blasts (RAEB), a somatic mutation of mitochondrial transfer RNA(Leu(UUR)) was detected in bone marrow cells. Heteroduplex analysis indicated that 40% to 50% of mitochondrial DNA (mtDNA) molecules in the bone marrow (BM) carried the novel G3242A mutation. The proportion of mutant mtDNA was higher in CD34(+) cells than in the unfractionated sample. Surprisingly, the mutation was not detectable by heteroduplex analysis in the peripheral blood (PB). However, PB CD34(+) cells selected by immunomagnetic beads harbored the mutation with a proportion of approximately 50%. In hematopoietic colony assays, CD34(+) cells from BM and PB yielded only colonies with wild-type mtDNA. These results indicate that the mtDNA mutation in CD34(+) cells was associated with a maturation defect. Mitochondrial tRNA mutations impair mitochondrial protein synthesis, thereby causing dysfunction of the mitochondrial respiratory chain. We propose that this effect contributed to ineffective hematopoiesis in our patient.

• Authors: Norbert Gattermann, Michael Wulfert, Bärbel Junge, Ulrich Germing, Rainer Haas, Götz Hofhaus
• Journal: Blood (Blood) Vol. 103 Issue 4 Pg. 1499-502 (Feb 15 2004) ISSN: 0006-4971 [Print] United States
• PMID: 14576046 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Transfer

Topics

• Aged
• Bone Marrow Cells (physiology)
• Hematopoiesis (genetics)
• Heteroduplex Analysis
• Humans
• Male
• Mitochondria (genetics)
• Myelodysplastic Syndromes (genetics)
• Point Mutation
• RNA, Transfer (genetics)