Laboratorio de Inmunología Oncológica, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Ciudad de Buenos Aires, Argentina.
Eur J Haematol. 2011 Jul;87(1):80-6. doi: 10.1111/j.1600-0609.2011.01613.x.
Richter's transformation of B-cell chronic lymphocytic leukemia (CLL) to cutaneous diffuse large B-cell lymphoma (DLBCL) is very rare. We took the advantage of one of these cases to test the hypothesis that the chemokine receptor CCR4 is involved in the homing of CLL cells to skin.
We evaluated CCR4 expression by flow cytometry in both circulating and skin CD19(+) leukemic cells from a patient with cutaneous DLBCL. As controls, we used peripheral blood samples from CLL patients without skin manifestations and from elderly healthy donors.
We found that both DLBCL cells derived from the original CLL clone and circulating CLL cells from this patient expressed CCR4. Although it was previously reported that CCR4 is not expressed in CLL cells, we found that a low but significant proportion of leukemic cells from CLL patients with no skin manifestations do express CCR4. There was a positive correlation between the expression of CCR4 and the percentage of ZAP-70 of each sample. Moreover, we consistently observed a higher expression of CCR4 within CD19(+)CD38(+) and CD19(+)Ki67(+) subsets compared to CD19(+)CD38(-) and CD19(+)Ki67(-) lymphocytes from the same sample, respectively.
We conclude that the chemokine receptor CCR4 is not a special feature of CLL cells with skin manifestation, but rather it is expressed in a low but significant proportion of peripheral blood CLL cells.
Richter 转化型 B 细胞慢性淋巴细胞白血病(CLL)向皮肤弥漫性大 B 细胞淋巴瘤(DLBCL)的转化非常罕见。我们利用其中一个病例来检验趋化因子受体 CCR4 参与 CLL 细胞向皮肤归巢的假说。
我们通过流式细胞术评估了一位患有皮肤 DLBCL 的患者的循环和皮肤 CD19(+)白血病细胞中 CCR4 的表达。作为对照,我们使用了无皮肤表现的 CLL 患者和老年健康供者的外周血样本。
我们发现源自原始 CLL 克隆的 DLBCL 细胞和该患者的循环 CLL 细胞均表达 CCR4。尽管之前有报道称 CCR4 不在 CLL 细胞中表达,但我们发现无皮肤表现的 CLL 患者的白血病细胞中有一小部分但显著表达 CCR4。每个样本的 CCR4 表达与 ZAP-70 的百分比之间存在正相关。此外,我们一致观察到,与同一样本的 CD19(+)CD38(-)和 CD19(+)Ki67(-)淋巴细胞相比,CD19(+)CD38(+)和 CD19(+)Ki67(+)淋巴细胞中 CCR4 的表达更高。
我们得出结论,趋化因子受体 CCR4 不是有皮肤表现的 CLL 细胞的特殊特征,而是在外周血 CLL 细胞中有一小部分但显著表达。