Mutation of mitochondria cytochrome oxidase gene in patients with myelodysplastic syndrome / 中国实验血液学杂志

ABSTRACT

The relationship between mitochondria gene mutation and hematological malignancies has been focusing on as a key point in recent studies. This study was aimed to investigate whether in patients with myelodysplastic syndrome (MDS) exists mitochoudria cytochrome oxidase COI and COII gene mutations different from normal tissues and to analyze whether these mutations are "hot spot" mutations. Eighteen MDS patients aged from 20 to 70 years old were brought into this study, including 2 of RA, 3 of RCMD, 7 of RAEB, 5 of AML (transformation from MDS), and 1 of MDS/MPD. The total DNA was extracted both from bone marrow cells and buccal cells of the same patients. A pair of primers was designed to amplify a fragment with 528 base pair (7181 - 7709) by PCR technique, which contained high frequency mutation area of cytochrome oxidase COI and COII gene based on the literature reports. The PCR products were purified and sequenced as bidirection to confirm if there is any mutation. The results of sequence of COI and COII gene from MDS patient bone marrow cells were compared with both the standard sequence from GenBank and the sequence from MDS patient buccal cells. The results showed that 3 single nucleotide changes in 528 bp cytochrome oxidase gene fragment from 18 MDS patients were confirmed. They were 7674 T-->C, 7353 A-->G, and an insert mutation of G at 7702. The former two mutations caused isoleucine-->methionine, and methionine-->viline. The 7702G ins was only confirmed with marrow cells in a patient, and caused a frame shift, which suggested that the mutation might be related to MDS cells. It is concluded that some of "hot spots" of mtDNA mutation in cytochrome oxidase (COI, COII) gene from our MDS patients are failed to be confirmed, but 3 new mutations on this gene are found, which suggested that mitochondria DNA mutations in MDS patients still have much complexity and heterogeneity, mtDNA mutation may be a prophase or an accompany phenomenon of this disease.