Strnad M, Brajuskovic G, Strelic N, Todoric-Zivanovic B, Stamatovic D, Tatomirovic Z, Magic Z
Institute of Pathology, Military Medical Academy, Belgrade, Serbia.
J BUON. 2008 Jul-Sep;13(3):403-8.
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease developing out of pluripotent hematopoietic stem cells that contain the fusion Bcr-Abl gene. The mechanisms that lead to these changes at molecular level are still unknown as are the mechanisms that increase the proliferative capacity of these cells. Disorders that occur in the process of apoptosis represent one of the possible molecular mechanisms that bring about disease progress. In our study we analyzed the presence of mutated (mut) p53 gene and the amplification of Bax proteins in patients with CML.
This study included 30 patients with CML (23 in chronic phase, 7 in blast transformation). Using immunohistochemistry with alkaline phosphatase / anti-alkaline phosphatase (APAAP) method we analyzed the expression of cell death proteins p53 and Bax in mononuclear bone marrow cells. Polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method was used to analyze the presence of mut p53 gene in mononuclear peripheral blood cells. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to analyze the presence of Bcr-Abl in peripheral blood cells.
High expression of Bax protein was detected in all analyzed patients, but no significant differences were noticed among them. No mut p53 gene was detected in any of the analyzed samples. Bcr-Abl b3a2 protein form was detected in all patients with variant translocations.
Lack of mut p53 product in the peripheral blood and bone marrow cells in patients with CML suggests that this gene plays no important role in disease pathology. Increased level of Bax protein expression is an essential characteristic of CML cells but it is not related with the clinical stage of disease.
慢性粒细胞白血病（CML）是一种起源于含有融合性Bcr - Abl基因的多能造血干细胞的恶性骨髓增殖性疾病。导致这些分子水平变化的机制以及增加这些细胞增殖能力的机制仍然未知。凋亡过程中出现的紊乱是导致疾病进展的可能分子机制之一。在我们的研究中，我们分析了CML患者中突变型（mut）p53基因的存在情况以及Bax蛋白的扩增情况。
本研究纳入了30例CML患者（23例处于慢性期，7例处于急变期）。使用碱性磷酸酶/抗碱性磷酸酶（APAAP）免疫组织化学方法，我们分析了单核骨髓细胞中细胞死亡蛋白p53和Bax的表达。采用聚合酶链反应单链构象多态性（PCR - SSCP）方法分析单核外周血细胞中mut p53基因的存在情况。采用逆转录 - 聚合酶链反应（RT - PCR）方法分析外周血细胞中Bcr - Abl的存在情况。
在所有分析的患者中均检测到Bax蛋白的高表达，但未观察到显著差异。在任何分析样本中均未检测到mut p53基因。在所有具有变异易位的患者中均检测到Bcr - Abl b3a2蛋白形式。
CML患者外周血和骨髓细胞中缺乏mut p53产物表明该基因在疾病病理学中不发挥重要作用。Bax蛋白表达水平升高是CML细胞的一个基本特征，但它与疾病的临床分期无关。
