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评估嘌呤类似物引起的慢性淋巴细胞白血病患者外周血和骨髓细胞凋亡与疾病进展参数的相关性。

Assessment of peripheral blood and bone marrow cells apoptosis caused by purine analogues in patients with chronic lymphocytic leukemia in correlation with parameters of disease progression.

机构信息

Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.

出版信息

Acta Haematol. 2010;123(3):171-8. doi: 10.1159/000294961. Epub 2010 Mar 11.

Abstract

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course and prognosis. Therefore, the role of prognostic factors is very important, especially for identifying the group of patients who require intensive treatment. The aim of this study was to assess whether the rate of apoptosis caused by purine analogues differs between patients with better or worse prognostic factors. The experiments were preformed in cultures of blood and bone marrow obtained from CLL patients. The cultures were supplemented with cladribine and fludarabine. We determined the percentage of caspase-3-positive cells and the BCL-2/BAX ratio, and subsequently these apoptosis markers were correlated with the expression of ZAP-70 and CD38, lymphocyte counts, lactate dehydrogenase and beta(2)-microglobulin levels and clinical stage according to the Rai classification. The results showed that bone marrow cells are more sensitive to apoptosis caused by purine analogues than cells derived from blood, supporting the idea that these two compartments have different proliferative statuses. The cells from ZAP-70-positive patients seem to enter apoptosis more readily than those from ZAP-70-negative patients; thus, ZAP-70-positive patients are more likely to benefit from treatment with purine analogues.

摘要

慢性淋巴细胞白血病(CLL)是一种异质性疾病,具有不同的临床病程和预后。因此,预后因素的作用非常重要,特别是对于确定需要强化治疗的患者群体。本研究旨在评估嘌呤类似物引起的细胞凋亡率在预后较好和较差的患者之间是否存在差异。实验在从 CLL 患者获得的血液和骨髓培养物中进行。培养物中添加了克拉屈滨和氟达拉滨。我们确定了 caspase-3 阳性细胞的百分比和 BCL-2/BAX 比值,随后根据 Rai 分类将这些凋亡标志物与 ZAP-70 和 CD38 的表达、淋巴细胞计数、乳酸脱氢酶和β2-微球蛋白水平以及临床分期相关联。结果表明,骨髓细胞比血液来源的细胞对嘌呤类似物引起的细胞凋亡更为敏感,这支持了这两个隔室具有不同增殖状态的观点。来自 ZAP-70 阳性患者的细胞似乎比来自 ZAP-70 阴性患者的细胞更容易进入凋亡状态;因此,ZAP-70 阳性患者更有可能从嘌呤类似物治疗中获益。

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