Pol Arch Intern Med. 2017 Apr 28;127(4):238-244. doi: 10.20452/pamw.3998. Epub 2017 Apr 20.
INTRODUCTION Currently available prognostic factors determining the course of chronic lymphocytic leukemia (CLL) are not fully efficient, especially for newly diagnosed patients. Investigation of molecular changes may help clarify the reasons for the heterogeneity of the disease. Apart from already confirmed TP53 mutations, the novel candidates: NOTCH1, SF3B1, and MYD88 might represent clinically relevant biomarkers. OBJECTIVES The aim of this study was to evaluate the mutational status of NOTCH1, MYD88, and SF3B1 and to compare the results with confirmed prognostic factors: ZAP‑70, CD38, and immunoglobulin heavy‑chain variable region (IGHV) mutation in CLL. The study assessed also prognostic significance in terms of the time to first treatment (TTFT) and subset analysis. PATIENTS AND METHODS The study was conducted on samples of 370 newly diagnosed patients with CLL. The analysis was performed using high‑resolution melting, Sanger sequencing, and polymerase chain reaction methods. RESULTS Patients harboring the NOTCH1 mutation were significantly more often found among patients with an unmutated IGHV gene status and high expression of CD38 and ZAP‑70. The MYD88 mutation was equally distributed in patients with mutated and unmutated IGHV status (5 vs 7 patients). For MYD88 and SF3B1, there were no significant differences in the levels of CD38 and ZAP‑70 expression. The tendency for lower median TTFT was revealed in patients with mutated SF3B1 (P = 0.08). The analysis showed the presence of 14 different types of the subsets of IGHV in 50 of 345 patients (14.5%). The most frequent were subsets #1 and #2. CONCLUSIONS The NOTCH1 and SF3B1 mutations accompany biological markers of unfavorable prognosis in patients with CLL. The mutations may contribute to the identification of patients with high‑risk CLL.
简介 当前用于确定慢性淋巴细胞白血病 (CLL) 病程的预后因素并不完全有效，尤其是对于新诊断的患者。对分子变化的研究可能有助于阐明疾病异质性的原因。除了已经证实的 TP53 突变外，新的候选基因：NOTCH1、SF3B1 和 MYD88 可能代表具有临床意义的生物标志物。 目的 本研究旨在评估 NOTCH1、MYD88 和 SF3B1 的突变状态，并将结果与已确认的预后因素：ZAP-70、CD38 和免疫球蛋白重链可变区 (IGHV) 突变进行比较。该研究还评估了在首次治疗时间 (TTFT) 和亚组分析方面的预后意义。 患者和方法 本研究纳入了 370 例新诊断的 CLL 患者的样本。使用高分辨率熔解曲线、Sanger 测序和聚合酶链反应方法进行分析。 结果 未突变 IGHV 基因状态和高表达 CD38 和 ZAP-70 的患者中，NOTCH1 突变的发生率明显更高。MYD88 突变在突变和未突变 IGHV 状态的患者中分布均匀（5 例与 7 例）。对于 MYD88 和 SF3B1，CD38 和 ZAP-70 的表达水平没有显著差异。SF3B1 突变患者的中位 TTFT 有降低的趋势（P=0.08）。分析显示，在 345 例患者中有 50 例（14.5%）存在 14 种不同类型的 IGHV 亚组。最常见的是亚组 #1 和 #2。 结论 NOTCH1 和 SF3B1 突变与 CLL 患者不良预后的生物学标志物有关。这些突变可能有助于识别高危 CLL 患者。
