Oka Tomomi, Nakajima Takeshi, Iwasaki Makoto, Takeda June, Torishima Masako, Sakurada Maki, Shimizu Takuya, Shindo Takero, Fujimoto Masakazu, Otsuki Shinya, Haga Hironori, Sugano Kokichi, Ando Miho, Mizumoto Chisaki, Kanda Junya, Nannya Yasuhito, Ogawa Seishi, Takaori-Kondo Akifumi, Kosugi Shinji
Clinical Genetics Unit Kyoto University Hospital Kyoto Japan.
Department of Hematology Graduate School of Medicine Kyoto University Kyoto Japan.
EJHaem. 2025 Jul 28;6(4):e70116. doi: 10.1002/jha2.70116. eCollection 2025 Aug.
Lynch syndrome (LS), which is an autosomal dominant disorder caused primarily by germline pathogenic variants of mismatch repair (MMR) genes, cases a number of malignancies. Hematologic malignancies are not included as related tumors of LS because it has not yet been established whether the carcinogenesis of hematologic malignancies is associated with MMR genes. A 75-year-old woman was admitted to our hospital with acute myeloid leukemia (AML) that had progressed from myelodysplastic syndrome (MDS). She had a history of multiple myeloma (MM) and multiple tumors associated with LS. Genetic testing revealed extensive homozygous deletions ranging from Exon 9 of to Exons 1-6 of . Finally, we diagnosed her with LS. It revealed that the homo-deletion occurred in myeloid cells after the onset of MM. Immunohistochemistry for MMR proteins on bone marrow specimens at MDS showed the loss of staining for the MSH2 and MSH6 proteins in myeloid cells. However, microsatellite instability was negative in spite of the large homozygous deletion of . It remains unclear whether the homo-deletion of is involved in the development of MDS/AML. Future studies are warranted to confirm the impact of MMR variants on the pathogenesis/chemoresistance of myeloid neoplasms. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
林奇综合征（LS）是一种常染色体显性疾病，主要由错配修复（MMR）基因的种系致病性变异引起，可导致多种恶性肿瘤。血液系统恶性肿瘤不被视为LS的相关肿瘤，因为血液系统恶性肿瘤的致癌作用是否与MMR基因相关尚未确定。一名75岁女性因从骨髓增生异常综合征（MDS）进展而来的急性髓系白血病（AML）入住我院。她有多发性骨髓瘤（MM）病史以及与LS相关的多种肿瘤病史。基因检测发现从 外显子9到 外显子1 - 6存在广泛的纯合缺失。最终，我们诊断她患有LS。结果显示MM发病后髓系细胞中出现 纯合缺失。MDS时骨髓标本MMR蛋白的免疫组化显示髓系细胞中MSH2和MSH6蛋白染色缺失。然而，尽管 存在大片段纯合缺失，微卫星不稳定性仍为阴性。 纯合缺失是否参与MDS/AML的发生发展仍不清楚。有必要进行进一步研究以证实MMR变异对髓系肿瘤发病机制/化疗耐药性的影响。试验注册：作者已确认本投稿无需临床试验注册。
