Assuntos
Crise Blástica , Proteínas de Fusão bcr-abl , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Crise Blástica/patologia , Crise Blástica/tratamento farmacológico , Humanos , Animais , Camundongos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-abl/genética , Niacinamida/análogos & derivadosRESUMO
To further clarify the role of ribosomal protein S14 (RPS14) in myelodysplastic syndrome, we examined RPS14 transcription in bone marrow derived CD34+ cells from patients with non-5q- myelodysplastic syndrome and found a reduced expression of RPS14 in 51 of 72 (71%) patients. MDS patients with an intermediate-1 risk (INT-1) score according to the international prognostic scoring system and low RPS14 expression had a superior median overall survival of not reached versus 25 months compared to INT-1 patients with high RPS14 expression (p=0.0249). Using multivariate analysis, the RPS14 expression status was confirmed as an independent predictor for survival in INT-1 patients.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 5/genética , Regulação Neoplásica da Expressão Gênica , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Proteínas Ribossômicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Sistema de Registros , Taxa de Sobrevida/tendênciasRESUMO
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.
