Purroy Noelia, Abrisqueta Pau, Carabia Júlia, Carpio Cecilia, Palacio Carles, Bosch Francesc, Crespo Marta
Laboratory of Experimental Hematology, Department of Hematology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Oncotarget. 2015 Apr 10;6(10):7632-43. doi: 10.18632/oncotarget.2939.
Chronic lymphocytic leukemia (CLL) cells residing in the bone marrow (BM) and in secondary lymphoid tissues receive survival and proliferative signals from the microenvironment, resulting in persistence of residual disease after treatment. In this study, we characterized primary CLL cells cultured with BM stromal cells, CD40 ligand and CpG ODN to partially mimic the microenvironment in the proliferative centers. This co-culture system induced proliferation and chemoresistance in primary CLL cells. Importantly, co-cultured primary CLL cells shared many phenotypical features with circulating proliferative CLL cells, such as upregulation of ZAP-70 and CD38 and higher CD49d and CD62L expression. This indicates aggressiveness and capability to interact with surrounding cells, respectively. In addition, levels of CXCR4 were decreased due to CXCR4 internalization after CXCL12 stimulation by BM stromal cells. We suggest that this co-culture system can be used to test drugs and their combinations that target the proliferative and drug resistant CLL cells.
存在于骨髓（BM）和二级淋巴组织中的慢性淋巴细胞白血病（CLL）细胞从微环境中获得生存和增殖信号，导致治疗后残留疾病持续存在。在本研究中，我们对与骨髓基质细胞、CD40配体和CpG ODN共同培养的原发性CLL细胞进行了表征，以部分模拟增殖中心的微环境。这种共培养系统诱导原发性CLL细胞增殖和产生化学抗性。重要的是，共培养的原发性CLL细胞与循环增殖性CLL细胞具有许多表型特征，例如ZAP-70和CD38上调以及更高的CD49d和CD62L表达。这分别表明了侵袭性和与周围细胞相互作用的能力。此外，由于骨髓基质细胞刺激CXCL12后CXCR4内化，CXCR4水平降低。我们建议该共培养系统可用于测试针对增殖性和耐药性CLL细胞的药物及其组合。
