Attia Hanaa R M, Ibrahim Mona Hamed, El-Aziz Shereen H Abd, Abdelrahman Amany H, Sobeih Mohamed Emam, Hagag Heba A A, Yassa Marianne E, Osman Randa A, Rawi Rasha, El-Dayem Omnia Y Abd, Elsharkawi Nahla, Abdelfattah Raafat, Hassan Naglaa M
Department of Clinical and Chemical Pathology, Medical Division, National Research Centre, Centre of Excellence, 12622 Cairo, Egypt.
Department of Medical Oncology, National Cancer Institute, 11796 Cairo, Egypt.
Mol Clin Oncol. 2021 May;14(5):100. doi: 10.3892/mco.2021.2262. Epub 2021 Mar 13.
The aim of the present study was to investigate different biological prognostic markers to identify high-risk patients with chronic lymphocytic leukemia (CLL) with a higher tumor burden, in order to ensure appropriate management. A total of 81 Egyptian patients with CLL were enrolled in the present study, with 75 healthy subjects serving as the control group. The expression of CD49d, CD38 and ZAP-70 in CLL cells was assessed using flow cytometry. The fluorescence hybridization technique was employed to evaluate (del17p), ataxia-telangiectasia (del11q) and (del13q14) genes and the presence of trisomy 12. The serological markers β2 microglobulin (B2M) and sCD23 were measured by ELISA. The gene was highly expressed in 25.9% and cytogenetic aberrations were observed in 66.6% of all recruited CLL patients. The patients were categorized according to the Binet staging system and a significant increase in the expression of sCD23, CD49d and ZAP-70 was detected in group C (P=0.008, 0.034 and 0.017, respectively) when compared to groups A and B. CD49d patients exhibited significantly higher expression of CD38 (P=0.002) and trisomy 12 (P=0.015) and lower expression of del13q14 (P=0.001). Patients who were CD49d with B2M>3.5 µg/ml exhibited higher total leukocyte count (P=0.048), higher absolute lymphocyte count (P=0.036), higher expression of CD38 (P=0.002) and trisomy 12 (P=0.034) and lower expression of del13q14 (P=0.002). Therefore, sCD23, CD49d and ZAP-70 may be considered as an optimal prognostic marker combination to be evaluated in the early stages of CLL and throughout disease management. Integrating both serological markers and CD49d expression by flow cytometry may add to the prognostic value of each marker alone and help identify high-risk patients with a higher tumor burden.
本研究的目的是调查不同的生物学预后标志物，以识别肿瘤负荷较高的慢性淋巴细胞白血病（CLL）高危患者，以确保适当的管理。本研究共纳入81例埃及CLL患者，75例健康受试者作为对照组。采用流式细胞术评估CLL细胞中CD49d、CD38和ZAP-70的表达。采用荧光杂交技术评估（del17p）、共济失调-毛细血管扩张（del11q）和（del13q14）基因以及12号三体的存在情况。采用ELISA法检测血清学标志物β2微球蛋白（B2M）和sCD23。在所招募的所有CLL患者中，该基因在25.9%的患者中高表达，66.6%的患者观察到细胞遗传学异常。根据Binet分期系统对患者进行分类，与A组和B组相比，C组sCD23、CD49d和ZAP-70的表达显著增加（P分别为0.008、0.034和0.017）。CD49d患者的CD38表达（P=0.002）和12号三体（P=0.015）显著更高，而del13q14表达更低（P=0.001）。B2M>3.5μg/ml的CD49d患者白细胞总数更高（P=0.048）、绝对淋巴细胞计数更高（P=0.036）、CD38表达更高（P=0.002）和12号三体更高（P=0.034），而del13q14表达更低（P=0.002）。因此，sCD23、CD49d和ZAP-70可被视为在CLL早期及整个疾病管理过程中进行评估的最佳预后标志物组合。将血清学标志物和流式细胞术检测的CD49d表达相结合，可能会增加每个标志物单独的预后价值，并有助于识别肿瘤负荷较高的高危患者。
