Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Crete, Greece.
Genet Mol Biol. 2013 Mar;36(1):7-11. doi: 10.1590/S1415-47572013005000003. Epub 2013 Mar 4.
It has been suggested that leukemia is characterized by an impaired balance between the proliferation of blood cells and their capacity to undergo apoptosis. The aim of this study was to examine the expression of key molecules related to apoptosis (BCL-2, BAX, FAS, FAS-L) in children with acute lymphoblastic leukemia (ALL). Measurement of BCL-2 and BAX mRNA was performed by quantitative real-time PCR, and membrane expression of FAS and FAS-L was assessed by flow cytometry in bone marrow mononuclear cells, both at diagnosis and at remission following induction chemotherapy. At diagnosis, increased levels of the apoptotic BAX/BCL-2 ratio were observed in children older than 10 years and with higher white blood cell counts. A DNA index < 1.16 was associated with increased BAX/BCL-2, both at diagnosis and at remission, and the del(9p) chromosome abnormality with increased BAX/BCL-2 at remission. The expression of the apoptotic receptor FAS was significantly higher at remission compared to diagnosis, which might reflect enhanced sensitivity of the leukemic clone to apoptosis and response to treatment. Altogether, our results highlight the association of apoptosis-related genes with clinical and cytogenetic prognostic parameters in pediatric ALL. A better understanding of the mechanisms and regulation of apoptosis should enable the design of novel targeted therapies for these patients.
有人提出，白血病的特征是血细胞增殖与其凋亡能力之间的失衡。本研究旨在检测急性淋巴细胞白血病（ALL）患儿中与凋亡相关的关键分子（BCL-2、BAX、FAS、FAS-L）的表达。通过定量实时 PCR 测量 BCL-2 和 BAX mRNA 的表达，通过流式细胞术测量骨髓单个核细胞中 FAS 和 FAS-L 的膜表达，分别在诊断时和诱导化疗缓解时进行。在诊断时，年龄大于 10 岁和白细胞计数较高的患儿中观察到凋亡 BAX/BCL-2 比值升高。DNA 指数 <1.16 与诊断时和缓解时的 BAX/BCL-2 升高有关，del(9p)染色体异常与缓解时的 BAX/BCL-2 升高有关。与诊断时相比，凋亡受体 FAS 在缓解时的表达显著升高，这可能反映了白血病克隆对凋亡的敏感性增强和对治疗的反应。总之，我们的研究结果强调了凋亡相关基因与儿科 ALL 临床和细胞遗传学预后参数的关联。更好地理解凋亡的机制和调控应该能够为这些患者设计新的靶向治疗。
