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易位(11;14)是单克隆免疫球蛋白沉积病克隆性浆细胞中常见的细胞遗传学异常。

Translocation (11;14) is a common cytogenetic abnormality in clonal plasma cells in monoclonal immunoglobulin deposition disease.

机构信息

Department of Hematology/Oncology, Columbia University Medical Center, New York City, New York, USA.

Department of Biostatistics, University of North Carolina, Durham, North Carolina, USA.

出版信息

Br J Haematol. 2024 Nov;205(5):1860-1865. doi: 10.1111/bjh.19748. Epub 2024 Sep 6.

Abstract

Monoclonal Immunoglobulin deposition disease (MIDD) is characterised by deposits of intact monoclonal light chains in the kidney leading to renal dysfunction. In this study, we retrospectively investigated the underlying plasma cell cytogenetic abnormalities in MIDD. CyclinD1 (11;14) translocation was identified in 12/27 (45%) patients. Among the patients without translocation, del13q and hyperdiploidy were the most common abnormalities. Patients in the non-t (11;14) group had a higher baseline light-chain ratio, higher proteinuria and lower eGFR as compared to patients with t (11;14). Haematological VGPR or higher was seen in 58% of t (11;14), and 30% without t (11;14), possibly related to higher use of Daratumumab-based therapy in the t (11;14) group. With a median follow-up of 750 days, 30% (8/24) progressed to end stage renal disease (ESRD). eGFR <20 mL/min (HR 25, 95% CI 2.09-298, p = 0.01) and 24 urine protein >3 g/24 h (HR 9, 95% CI 1.27-63.90, p = 0.02) at diagnosis were significantly associated with progression to ESRD. Renal survival was better in t (11;14) as compared to the non-t (11;14) group (HR 0.11, p = 0.06). Translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Identification of this abnormality should lead to exploration of BCL2 inhibitors in this disease.

摘要

单克隆免疫球蛋白沉积病(MIDD)的特征是完整的单克隆轻链在肾脏中沉积,导致肾功能障碍。在本研究中,我们回顾性研究了 MIDD 患者的浆细胞细胞遗传学异常。12/27(45%)患者存在 cyclinD1(11;14)易位。在无易位的患者中,del13q 和超二倍体是最常见的异常。与 t(11;14)患者相比,非 t(11;14)组患者的基线轻链比值更高、蛋白尿更多、eGFR 更低。t(11;14)组中有 58%的患者达到血液学 VGPR 或更高,而无 t(11;14)组中有 30%的患者达到该疗效,这可能与 t(11;14)组中更多使用达雷妥尤单抗治疗有关。中位随访 750 天后,30%(8/24)进展至终末期肾病(ESRD)。诊断时 eGFR <20 mL/min(HR 25,95%CI 2.09-298,p=0.01)和 24 小时尿蛋白 >3 g/24 h(HR 9,95%CI 1.27-63.90,p=0.02)与进展为 ESRD 显著相关。与非 t(11;14)组相比,t(11;14)组的肾脏生存率更好(HR 0.11,p=0.06)。易位(11;14)是 MIDD 的常见异常,影响其临床表现和预后。识别这种异常应导致在该疾病中探索 BCL2 抑制剂。

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