骨髓增生异常综合征急性髓系白血病变伴t(3;5)(q25;q34)染色体易位分子特征的研究

Objective To investigate the molecular characteristics t(3;5(q25;q34) chromosome translocation. Method A case of t(3;5)(q25;q34) acute myeloid leukemia secondary to myelodysplastic syndrome was reported. Karyotype analysis was performed by R banding technique and chromosome 3 and 5 painting. The expression of NPM-MLF1 fusion gene and MLF1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR). NPM gene mutation was analyzed by PCR combined with sequencing. The Evi-1 and MDS1/ Evi-1 genes expression were examined by fluorescent Real-time PCR. The subcellular localization of wild MLF1 and NPM-MLF1 proteins were determined by immunohistochemistry staining. bcl-2 proteins were detected by Western blot. Results t (3;5)(q25;q34) chromosome translocation was confirmed by both R banding and chromosome painting, NPM-MLF1 fusion gene was positive and become negative after chemotherapy. The non-coding alternative splicings of MLF1 gene were detected in the patient’s leukemic cells, and Evi-1 gene was negative and MDS1/Evi-1 expression was dim. No mutations were found in NPM gene, and bcl2 protein was also negative. the wild MLF1 protein was localized to the cytoplasm, whereas the NPM-MLF1 fusion protein was almost exclusively nucleolar in the leukemic cells. Conclution t (3;5)(q25;q34) is a rare nonrandom chromosome abnormality of myeloid tumors, NPM-MLF1 fusion gene is the molecular basis of the pathogenesis of myeloid tumors with t (3;5)(q25;q34) chromosome translocation.