目的:体质染色体畸变在血液系统恶性肿瘤中很少见,其致病作用大多知之甚少。我们提出了在两个兄弟姐妹-姐妹-诊断为骨髓增生异常综合征(MDS)中发现的新型结构性染色体易位的综合分子特征。
方法:使用G显带检查两名患者的骨髓和血细胞,RNA测序,PCR,还有Sanger测序.
结果:我们在两个兄弟姐妹骨髓中发现了平衡的t(17;19)(q21;p13)易位,血细胞,和植物血凝素刺激的淋巴细胞。易位在der(19)t(17;19)上产生了MYO1F::WNK4嵌合体,编码嵌合丝氨酸/苏氨酸激酶,和der上的VPS25::MYO1F(17),可能导致VPS25蛋白异常。
结论:在两姐妹中发现的t(17;19)(q21;p13)易位可能使他们易患骨髓增生异常。MYO1F::WNK4和/或VPS25::MYO1F嵌合体,也许尤其是编码嵌合丝氨酸/苏氨酸激酶的MYO1F::WNK4,在MDS发病机制中发挥作用,仍然不完全理解。
OBJECTIVE: Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).
METHODS: Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing.
RESULTS: We identified a balanced t(17;19)(q21;p13) translocation in both siblings\' bone marrow, blood cells, and phytohemagglutinin-stimulated lymphocytes. The translocation generated a MYO1F::WNK4 chimera on the der(19)t(17;19), encoding a chimeric serine/threonine kinase, and a VPS25::MYO1F on the der(17), potentially resulting in an aberrant VPS25 protein.
CONCLUSIONS: The t(17;19)(q21;p13) translocation found in the two sisters probably predisposed them to myelodysplasia. How the MYO1F::WNK4 and/or VPS25::MYO1F chimeras, perhaps especially MYO1F::WNK4 that encodes a chimeric serine/threonine kinase, played a role in MDS pathogenesis, remains incompletely understood.