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THE SIGNS OF NEGATIVE SELECTION IN IGHV FRAMEWORK REGIONS ARE ASSOCIATED WITH WORSE OVERALL SURVIVAL OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Leukemia Research ( IF 2.1 ) Pub Date : 2021-08-25 , DOI: 10.1016/j.leukres.2021.106686
Iryna Abramenko 1 , Nadia Bilous 1 , Anatoliy Chumak 1 , Iryna Kryachok 2 , Zoya Fedorenko 3 , Zoya Martina 4 , Iryna Dyagil 4
Affiliation  

The mutational status of the variable region of the immunoglobulin heavy chain (IGHV) genes remains the most significant prognostic factor in chronic lymphocytic leukemia (CLL) patients. However, the groups of mutated (M) and unmutated (UM) patients are also heterogeneous, and additional markers are used for a more accurate prognosis. The aim of our work was to determine the prognostic value of the signs of antigen selection determined by BASELINe statistics in M IGHV sequences of CLL patients. Clinical data, IGHV gene configuration, TP53, NOTCH1, SF3B1 mutations were analyzed in 127 CLL patients with M IGHV sequences. The median OS of patients with negative selection in the framework regions (FWRs) of IGHV genes was 120 months compared to 202 month in other CLL patients (P = 0.016). In multivariate Cox regression analysis Binet stage C vs A + B (P < 0.0001), SF3B1 mutations (P < 0.0001), negative selection in the FWRs (HR P = 0.007), and age ≥65 years (P = 0.034) were powerful adverse prognostic factors for OS in CLL patients with M IGHV genes. These preliminary data suggest that the signs of antigen-driven selection may be used as a prognostic factor in CLL patients with M IGHV genes in combination with other markers.



中文翻译:

IGHV 框架区域的阴性选择迹象与慢性淋巴细胞白血病患者的总体生存率较差有关

免疫球蛋白重链(IGHV)基因可变区的突变状态仍然是慢性淋巴细胞白血病(CLL)患者最重要的预后因素。然而,突变 (M) 和未突变 (UM) 患者组也是异质性的,额外的标志物用于更准确的预后。我们工作的目的是确定在CLL 患者的M IGHV序列中由基线统计确定的抗原选择迹象的预后价值。对 127 例 M IGHV CLL 患者的临床数据、IGHV基因配置、TP53NOTCH1SF3B1突变进行分析序列。IGHV基因框架区 (FWR) 阴性选择患者的中位 OS为 120 个月,而其他 CLL 患者为 202 个月(P  = 0.016)。在多变量 Cox 回归分析中,Binet C 期 vs A + B 期(P  < 0.0001)、SF3B1突变(P  < 0.0001)、FWR 中的负选择(HR P  = 0.007)和年龄≥65 岁(P  = 0.034)是强有力的具有 M IGHV基因的CLL 患者 OS 的不良预后因素。这些初步数据表明,抗原驱动选择的迹象可作为 M IGHV 的CLL 患者的预后因素 基因与其他标记结合。

更新日期:2021-08-26
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