IKAROS, encoded by is a tumor suppressor and a key hematopoietic transcription factor responsible for lymphoid and myeloid differentiation. mutations result in inborn errors of immunity presenting with increased susceptibility to infections, immune dysregulation, and malignancies. In particular, patients carrying gain-of-function (GOF) mutations mostly exhibit symptoms of immune dysregulation and polyclonal plasma cell proliferation. Herein, we describe seven new IKAROS GOF cases from two unrelated families, presenting with novel infectious, immune dysregulation and hematologic diseases. Two of the patients underwent allogeneic hematopoietic cell transplantation (HCT) due to poorly responsive complications. HCT was well-tolerated achieving full engraftment in both patients receiving reduced intensity, matched unrelated donor grafts, with no severe acute or chronic graft-vs-host-disease, and in remission from their diseases 2.5 and 4 years post-HCT, respectively. These results suggest that HCT is a valid and curative option in patients with IKAROS GOF disease and severe clinical manifestations.

中文翻译：

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IKAROS 功能获得性疾病：同种异体造血细胞移植经验和扩展的临床表型

IKAROS 编码的肿瘤抑制因子和负责淋巴和骨髓分化的关键造血转录因子。突变会导致先天性免疫缺陷，表现为对感染、免疫失调和恶性肿瘤的易感性增加。特别是，携带功能获得（GOF）突变的患者大多表现出免疫失调和多克隆浆细胞增殖的症状。在此，我们描述了来自两个不相关家庭的 7 例新的 IKAROS GOF 病例，表现为新的传染性、免疫失调和血液系统疾病。其中两名患者因并发症反应不佳而接受了同种异体造血细胞移植（HCT）。HCT 耐受性良好，在接受降低强度、匹配无关供体移植物、没有严重急性或慢性移植物抗宿主病的两名患者中实现了完全移植，并且分别在 HCT 后 2.5 年和 4 年疾病得到缓解。这些结果表明，HCT 对于 IKAROS GOF 疾病和严重临床表现的患者来说是一种有效且治愈的选择。