Sato Yuki, Koyama Daisuke, Yamada Shoki, Kamei Naomi, Fukuchi Koichiro, Suzuki Kengo, Uchida Yasuhiro, Suzuki Manabu, Fukatsu Masahiko, Hashimoto Yuko, Ikezoe Takayuki
Department of Hematology, Fukushima Medical University.
Department of Diagnostic Pathology, Fukushima Medical University.
Fukushima J Med Sci. 2025 Apr 19;71(2):129-134. doi: 10.5387/fms.24-00044. Epub 2025 Feb 8.
H3K4 methylation, primarily mediated by MLL family proteins, plays a pivotal role in the epigenetic regulation of gene transcription. Among the MLL family, KMT2A is known for its critical role in hematopoiesis. MLL family proteins feature C-terminal SET catalytic domains, requiring the formation of MLL complexes with proteins like DPY30 to maximize their enzymatic activity. Deletion of DPY30 results in a significant reduction in H3K4me1, H3K4me2, and H3K4me3 levels in bone marrow (BM) cells, underscoring the essential role of DPY30 in facilitating optimal catalytic activity within MLL family complexes. Here, we present a unique case of myelodysplastic neoplasms (MDS) associated with a novel t(2;19)(p23;q13.3) translocation. A 22-year-old pregnant woman initially sought consultation due to thrombocytopenia, which temporarily improved following a miscarriage. However, she later presented with progressive pancytopenia. RNA sequencing analysis of BM mononuclear cells using STAR-Fusion revealed the translocation breakpoint on chromosomes, resulting in the disruption of the DPY30 and CEACAM6 genes. BM failure showed marked improvement following cord blood transplantation. This case represents a novel form of MDS associated with the disruption of the DPY30 gene. Our findings underscore the importance of considering early hematopoietic stem cell transplantation for MDS cases attributed to DPY30 dysfunction.
H3K4甲基化主要由MLL家族蛋白介导，在基因转录的表观遗传调控中起关键作用。在MLL家族中，KMT2A因其在造血过程中的关键作用而闻名。MLL家族蛋白具有C端SET催化结构域，需要与DPY30等蛋白形成MLL复合物以最大化其酶活性。删除DPY30会导致骨髓（BM）细胞中H3K4me1、H3K4me2和H3K4me3水平显著降低，这突出了DPY30在促进MLL家族复合物内最佳催化活性方面的重要作用。在此，我们报告了一例与新型t(2;19)(p23;q13.3)易位相关的骨髓增生异常肿瘤（MDS）的独特病例。一名22岁孕妇最初因血小板减少症前来咨询，流产后血小板减少症暂时有所改善。然而，她后来出现进行性全血细胞减少。使用STAR-Fusion对BM单核细胞进行RNA测序分析揭示了染色体上的易位断点，导致DPY30和CEACAM6基因中断。脐血移植后BM衰竭明显改善。该病例代表了一种与DPY30基因中断相关的新型MDS。我们的研究结果强调了对于归因于DPY30功能障碍的MDS病例考虑早期造血干细胞移植的重要性。
