Kubota Yusuke, Sakurai Masatoshi, Nannya Yasuhito, Kogure Yasunori, Shiroshita Kohei, Fujita Shinya, Yamaguchi Kentaro, Mizuno Kota, Kato Jun, Mori Takehiko, Ogawa Seishi, Kataoka Keisuke
Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan.
Ann Hematol. 2024 Dec;103(12):5989-5998. doi: 10.1007/s00277-024-06123-x. Epub 2024 Dec 12.
Transient abnormal myelopoiesis (TAM) generally affects newborns with Down syndrome and is associated with constitutional trisomy 21 and a somatic GATA1 mutation. Here we describe a case of TAM which evolved after umbilical cord blood transplantation (UCBT), whose origin was identified as a GATA1 mutation-harboring clone in umbilical cord blood (UCB) by detailed genetic analyses. A 58-year-old male who received UCBT for peripheral T-cell lymphoma presented progressive anemia and thrombocytopenia, and leukocytosis with blast cells in the peripheral blood (PB). Bone marrow (BM) aspiration showed granulocytic and megakaryocytic dysplasia with excess blasts whose karyotype was trisomy 21. Short tandem repeat analysis showed complete donor chimerism. He was initially diagnosed as donor-derived myelodysplastic syndrome (MDS) and treated with azacitidine, followed by secondary transplantation using unrelated BM, providing durable complete remission. Retrospective targeted-capture sequencing analysis of PB/BM samples collected at multiple timepoints identified trisomy 21 and a GATA1 mutation, suggestive of a diagnosis of donor cell-derived TAM (DC-TAM). Importantly, a minor clone with the same GATA1 mutation was detected in UCB by droplet digital PCR. DC-TAM is a rare UCBT-related complication which resembles MDS, but the identification of GATA1 mutation may be useful for its diagnosis. Our genetic analyses revealed that a pre-existing clone in UCB may contribute to the development of donor cell-derived hematologic neoplasms, highlighting the potential relevance of genetic screening of donor UCB.
短暂异常髓系造血（TAM）通常影响唐氏综合征新生儿，与21号染色体三体及体细胞GATA1突变相关。本文描述了1例脐带血移植（UCBT）后发生的TAM病例，通过详细的基因分析确定其起源为脐带血（UCB）中携带GATA1突变的克隆。1例58岁男性因外周T细胞淋巴瘤接受UCBT，出现进行性贫血和血小板减少，外周血（PB）中出现原始细胞增多的白细胞增多症。骨髓穿刺显示粒细胞和巨核细胞发育异常伴原始细胞增多，其核型为21号染色体三体。短串联重复序列分析显示完全供体嵌合。他最初被诊断为供体来源的骨髓增生异常综合征（MDS），接受阿扎胞苷治疗，随后使用无关供体骨髓进行二次移植，实现持久完全缓解。对多个时间点采集的PB/BM样本进行回顾性靶向捕获测序分析，发现21号染色体三体和GATA1突变，提示诊断为供体细胞来源的TAM（DC-TAM）。重要的是，通过液滴数字PCR在UCB中检测到具有相同GATA1突变的微小克隆。DC-TAM是一种罕见的与UCBT相关的并发症，类似于MDS，但GATA1突变的鉴定可能有助于其诊断。我们的基因分析表明，UCB中预先存在的克隆可能促成供体细胞来源的血液肿瘤的发生，突出了供体UCB基因筛查的潜在相关性。
