Abadi Uri, Weisz Avivit, Kidron Dvora, Katzav Aviva, Hercbergs Aleck, Davis Paul J, Ellis Martin H, Ashur-Fabian Osnat
Translational Hemato-Oncology Laboratory, Hematology Institute and Blood Bank Meir Medical Center, Kfar-Saba 44821, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
J Clin Med. 2021 Apr 19;10(8):1766. doi: 10.3390/jcm10081766.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. The thyroid hormones, T3 and T4, bind the αvβ3 integrin and activate phosphorylates ERK (pERK). These tumor-promoting actions were reported in a number of malignancies, but not in CLL.
Primary cells from 22 CLL patients were verified for disease markers (CD5/CD19/CD23) and analyzed for αvβ3 by flow cytometry (FC), ImageStream, Western blots (WB), and immunohistochemistry (IHC) in archival bone marrow (BM, = 6) and lymph node (LN, = 5) tissues. Selected samples ( = 8) were incubated with T3 (1-100 nM) or T4 (0.1-10 µM) for 30 min, and the expression levels of αvβ3, pERK and PCNA (cell proliferation marker) were determined (WB).
αvβ3 was detected on the membrane of circulating CLL cells and in the BM but not in the LN. T3 and T4 enhanced αvβ3 protein levels in primary CLL cells. Similarly, pERK and PCNA were rapidly induced in response to T3 and T4 exposure.
αvβ3 integrin is expressed on primary CLL cells and is induced by thyroid hormones. We further suggest that the hormones are mitogenic in these cells, presumably via αvβ3-mediated signaling.
慢性淋巴细胞白血病（CLL）是最常见的成人白血病。甲状腺激素T3和T4与αvβ3整合素结合并激活磷酸化细胞外信号调节激酶（pERK）。这些促肿瘤作用在多种恶性肿瘤中均有报道，但在CLL中未见报道。
对22例CLL患者的原代细胞进行疾病标志物（CD5/CD19/CD23）验证，并通过流式细胞术（FC）、图像流式细胞仪、蛋白质免疫印迹法（WB）和免疫组织化学（IHC）对存档骨髓（BM，n = 6）和淋巴结（LN，n = 5）组织中的αvβ3进行分析。选取部分样本（n = 8）用T3（1 - 100 nM）或T4（0.1 - 10 μM）孵育30分钟，然后测定αvβ3、pERK和增殖细胞核抗原（PCNA，细胞增殖标志物）的表达水平（WB）。
在循环CLL细胞的细胞膜和骨髓中检测到αvβ3，但在淋巴结中未检测到。T3和T4可提高原代CLL细胞中αvβ3蛋白水平。同样，T3和T4处理后可迅速诱导pERK和PCNA表达。
αvβ3整合素在原代CLL细胞上表达，并受甲状腺激素诱导。我们进一步认为，这些激素在这些细胞中具有促有丝分裂作用，可能是通过αvβ3介导的信号传导实现的。
