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中国慢性淋巴细胞白血病患者的IGH易位:临床病理特征与基因图谱

IGH Translocations in Chinese Patients With Chronic Lymphocytic Leukemia: Clinicopathologic Characteristics and Genetic Profile.

作者信息

Li Qinlu, Xing Shugang, Zhang Heng, Mao Xiao, Xiao Min, Wang Ying

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Oncol. 2022 Jun 2;12:858523. doi: 10.3389/fonc.2022.858523. eCollection 2022.

Abstract

Immunoglobulin heavy chain translocations (IGH-t) have occasionally been reported in Chinese patients with chronic lymphocytic leukemia (CLL). The objective of the present study was to identify the clinicopathologic features of patients with IGH-t CLL and compare them with those of patients with non-IGH-t CLL. We performed fluorescence hybridization (FISH) based on a routine CLL prognostic FISH panel using IGH, IGH-BCL2, , IGH-CMYC, and FISH probes. Furthermore, we retrospectively evaluated the clinical features of 138 newly diagnosed CLL patients chromosome banding analysis (CBA), FISH, and targeted next-generation sequencing. IGH-t was identified in 25 patients (18.1%). Patients with IGH-t CLL had lower flow scores than those with non-IGH-t CLL. The most frequent translocation was t(14;18) (10 patients), followed by t(14;19) (3 patients), and t(2;14)(p13;q32), t(7;14)(q21.2;q12), t(9;14)(p13;q32) (3 patients). The remaining nine patients included three with abnormal karyotypes without translocation involving 14q32, four with a normal karyotype, and two who failed CBA. The most frequently concomitant FISH-detected aberrations were 13q deletion, followed by +12 and deletion, while one case involved deletion. Complex karyotypes were detected in five patients with IGH-t CLL, in whom all partner genes were non-. Available mutational information indicated that mutation was the most frequent mutation among tested 70 patients, while mutation was the most frequent mutation in the IGH-t group. Moreover, the IGH-t group had higher (P=0.014) and (P=0.004) mutations than the non-IGH-t group, and this difference was statistically significant. Our study demonstrates that IGH-t is not uncommon among Chinese CLL patients, and that its partner genes are multiple. The gene mutational profile of the IGH-t group was distinct from that of the non-IGH-t group, and the concomitant chromosomal abnormalities within the IGH-t CLL group differed. Thus, identification of IGH-t and its partner genes in CLL patients may help further refine risk stratification and strengthen the accurate management in CLL patients.

摘要

免疫球蛋白重链易位(IGH-t)在中国慢性淋巴细胞白血病(CLL)患者中偶有报道。本研究的目的是确定IGH-t CLL患者的临床病理特征,并将其与非IGH-t CLL患者的特征进行比较。我们基于常规的CLL预后荧光原位杂交(FISH)检测板,使用IGH、IGH-BCL2、IGH-CMYC和FISH探针进行了荧光杂交。此外,我们回顾性评估了138例新诊断的CLL患者的临床特征,采用染色体核型分析(CBA)、FISH和靶向二代测序。在25例患者(18.1%)中检测到IGH-t。IGH-t CLL患者的流式细胞术评分低于非IGH-t CLL患者。最常见的易位是t(14;18)(10例患者),其次是t(14;19)(3例患者),以及t(2;14)(p13;q32)、t(7;14)(q21.2;q12)、t(9;14)(p13;q32)(各3例患者)。其余9例患者包括3例核型异常但不涉及14q32易位的患者、4例核型正常的患者以及2例CBA检测失败的患者。FISH检测到的最常见伴随异常是13q缺失,其次是+12和缺失,而1例患者涉及缺失。在5例IGH-t CLL患者中检测到复杂核型,其中所有伙伴基因均为非。可用的突变信息表明,在70例检测患者中,突变是最常见的突变,而在IGH-t组中,突变是最常见的突变。此外,IGH-t组的(P=0.014)和(P=0.004)突变高于非IGH-t组,且这种差异具有统计学意义。我们的研究表明,IGH-t在中国CLL患者中并不罕见,其伙伴基因多样。IGH-t组的基因突变谱与非IGH-t组不同,且IGH-t CLL组内伴随的染色体异常也有所差异。因此,在CLL患者中鉴定IGH-t及其伙伴基因可能有助于进一步优化风险分层,并加强对CLL患者的精准管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/496b/9201519/32e2524e7627/fonc-12-858523-g001.jpg

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