Li Qinlu, Xing Shugang, Zhang Heng, Mao Xiao, Xiao Min, Wang Ying
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2022 Jun 2;12:858523. doi: 10.3389/fonc.2022.858523. eCollection 2022.
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.
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。