Del Giglio A, O'Brien S, Ford R J, Manning J, Saya H, Keating M, Johnston D, Chamone D F, Deisseroth A B
Department of Hematology, Sao Paulo University Medical School.
Leuk Lymphoma. 1993 Jul;10(4-5):265-71. doi: 10.3109/10428199309148548.
Chronic Lymphocytic Leukemia (CLL) is usually an indolent disorder which in some patients assumes an aggressive clinical course. In order to assess at presentation the prognosis of a given patient, several staging systems and prognostic variables have been proposed including the expression of the Proliferating Cell Nuclear Antigen (PCNA). PCNA is a 36 kd nuclear protein, the regulation of which is cell cycle-dependent. In CLL, PCNA levels correlate with cell proliferation, clinical stage and the lymphocyte doubling time (LDT). Furthermore, preliminary data suggests that PCNA expression may also predict response to Fludarabine-based chemotherapy. Since PCNA is a cofactor for Delta DNA polymerase, PCNA overexpression in CLL may also reflect the intrinsic DNA repair activity of the leukemic cells and thus their resistance to chemotherapy. Further studies aiming at modulation of PCNA expression in CLL cells may clarify this issue and may offer a future new therapeutic strategy with which to treat this disorder.
慢性淋巴细胞白血病(CLL)通常是一种惰性疾病,但在一些患者中会呈现侵袭性临床病程。为了在初诊时评估特定患者的预后,已提出了多种分期系统和预后变量,包括增殖细胞核抗原(PCNA)的表达。PCNA是一种36kd的核蛋白,其调节依赖于细胞周期。在CLL中,PCNA水平与细胞增殖、临床分期和淋巴细胞倍增时间(LDT)相关。此外,初步数据表明PCNA表达也可能预测对氟达拉滨为基础的化疗的反应。由于PCNA是δDNA聚合酶的辅因子,CLL中PCNA的过表达也可能反映白血病细胞的内在DNA修复活性,从而反映其对化疗的耐药性。旨在调节CLL细胞中PCNA表达的进一步研究可能会阐明这一问题,并可能提供一种未来治疗该疾病的新策略。