PDF(Pubmed)
Abstract：
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.
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.
摘要：
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。
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。
