Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome.
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.
Gattermann
Norbert
N
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Moorenstr 5, D-40225 Düsseldorf, Germany. gattermann@med.uni-duesseldorf.de
Wulfert
Michael
M
Junge
Bärbel
B
Germing
Ulrich
U
Haas
Rainer
R
Hofhaus
Götz
G
D000368:Aged; D001854:Bone Marrow Cells / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics*; D020180:Heteroduplex Analysis; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D017354:Point Mutation; D012343:RNA, Transfer / Q000235:genetics*
D012343:RNA, Transfer