Department of Cytology, Histology and Pathological Anatomy (Giga-R), University of Liege, Liège, Belgium.
PLoS One. 2011;6(10):e25651. doi: 10.1371/journal.pone.0025651. Epub 2011 Oct 3.
It is suspected that bone marrow (BM) microenvironmental factors may influence the evolution of chronic myeloid leukaemia (CML). In this study, we postulated that adipocytes and lipids could be involved in the progression of CML. To test this hypothesis, adipocytes were co-cultured with two BCR-ABL positive cell lines (PCMDS and K562). T cell (Jurkat) and stroma cell (HS-5) lines were used as controls. In the second set of experiments, leukemic cell lines were treated with stearic, oleic, linoleic or α-linolenic acids in presence or absence of leptin. Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression have been tested after 24h, 48h and 72h of treatment. Our results showed that adipocytes induced a decrease of CML proliferation and an increase in lipid accumulation in leukemic cells. In addition, CML cell lines induced adipocytes cell death. Chromatography analysis showed that BM microenvironment cells were full of saturated (SFA) and monounsaturated (MUFA) fatty acids, fatty acids that protect tumor cells against external agents. Stearic acid increased Bcl-2 expression in PCMDS, whereas oleic and linoleic acids had no effects. In contrast, α-linolenic acid decreased the proliferation and the survival of CML cell lines as well as BCL-2 and OB-R expression. The effect of α-linolenic acids seemed to be due to PI3K pathway and Bcl-2 inhibition. Leptin production was detected in the co-culture medium. In the presence of leptin, the effect of α-linolenic acid on proliferation, survival, OB-R and BCl-2 expression was reduced.
据推测，骨髓（BM）微环境因素可能影响慢性髓性白血病（CML）的演变。在这项研究中，我们假设脂肪细胞和脂质可能参与 CML 的进展。为了验证这一假设，我们将脂肪细胞与两种 BCR-ABL 阳性细胞系（PCMDS 和 K562）共培养。T 细胞（Jurkat）和基质细胞（HS-5）系被用作对照。在第二组实验中，在有或没有瘦素的情况下，用硬脂酸、油酸、亚油酸或α-亚麻酸处理白血病细胞系。在处理 24、48 和 72 小时后，检测了细胞的存活、增殖、瘦素产生、OB-R 同工型（OB-Ra 和 OB-Rb）、磷酸肌醇 3-激酶（PI3k）和 BCL-2 的表达。我们的结果表明，脂肪细胞诱导 CML 增殖减少和白血病细胞中脂质积累增加。此外，CML 细胞系诱导脂肪细胞死亡。色谱分析表明，BM 微环境细胞富含饱和（SFA）和单不饱和（MUFA）脂肪酸，这些脂肪酸能保护肿瘤细胞免受外部因素的侵害。硬脂酸增加了 PCMDS 中的 Bcl-2 表达，而油酸和亚油酸则没有影响。相反，α-亚麻酸降低了 CML 细胞系的增殖和存活，以及 BCL-2 和 OB-R 的表达。α-亚麻酸的作用似乎是由于 PI3K 途径和 Bcl-2 抑制。在共培养培养基中检测到瘦素的产生。在瘦素存在的情况下，α-亚麻酸对增殖、存活、OB-R 和 BCl-2 表达的作用降低。
