Cerveró C, Escribano L, San Miguel J F, Díaz-Agustín B, Bravo P, Villarrubia J, García-Sanz R, Velasco J L, Herrera P, Vargas M, González M, Navarro J L, Orfao A
Servicio de Hematología, Hospital Ramón y Cajal, Madrid, Spain.
Am J Hematol. 1999 Mar;60(3):191-5. doi: 10.1002/(sici)1096-8652(199903)60:3<191::aid-ajh4>3.0.co;2-y.
Bcl-2 protein plays a major role in the prevention of programmed cell death of differentiating cells. In the present study, the expression of cytoplasmic bcl-2 by human Bone Marrow Mast Cells (BMMC) from both normal and pathological bone marrow samples was examined. A total of 35 subjects corresponding to 9 healthy volunteers, 8 cases of adult indolent systemic mast cell disease (SMCD), 4 cases of pediatric mastocytosis (PM), 11 cases of hematological malignancies (HM), 2 cases of reactive bone marrow, and 1 case of mast cell leukemia (MCL) were analyzed. The expression of bcl-2 was studied using quantitative three-color flow cytometry. We also studied the molecular configuration of the bcl-2 gene and other relatives by Southern blot and polymerase chain reaction (PCR) in the MCL case. Bcl-2 expression was detected in BMMC from all samples analyzed. No significant differences on the expression of bcl-2 were detected between BMMC from healthy subjects and patients with SMCD, PM, HM, and reactive bone marrow. By contrast, bcl-2 protein was overexpressed in BMMC from MCL patient without gene rearrangement. Our results show that bcl-2 protein was constitutively expressed by BMMC. BMMC from MCL display overexpression of bcl-2, which could not be related to molecular rearrangements involving the bcl-2 gene. The expression of this protein by mature MC may play a role in the prevention of MC apoptosis and thus help to explain the long survival of these cells. The overexpression of bcl-2 by BMMC in MCL may help to explain their resistance to chemotherapy-induced apoptosis.
Bcl-2蛋白在防止分化细胞的程序性细胞死亡中起主要作用。在本研究中，检测了来自正常和病理骨髓样本的人骨髓肥大细胞（BMMC）中细胞质bcl-2的表达。共分析了35名受试者，包括9名健康志愿者、8例成人惰性系统性肥大细胞病（SMCD）、4例儿童肥大细胞增多症（PM）、11例血液系统恶性肿瘤（HM）、2例反应性骨髓病例和1例肥大细胞白血病（MCL）。使用定量三色流式细胞术研究bcl-2的表达。我们还通过Southern印迹和聚合酶链反应（PCR）研究了MCL病例中bcl-2基因及其他相关基因的分子构型。在所有分析样本的BMMC中均检测到Bcl-2表达。健康受试者与SMCD、PM、HM和反应性骨髓患者的BMMC之间，bcl-2表达未检测到显著差异。相比之下，未发生基因重排的MCL患者的BMMC中bcl-2蛋白过表达。我们的结果表明，BMMC组成性表达bcl-2蛋白。MCL患者的BMMC显示bcl-2过表达，这可能与涉及bcl-2基因的分子重排无关。成熟肥大细胞中该蛋白的表达可能在防止肥大细胞凋亡中起作用，从而有助于解释这些细胞的长期存活。MCL中BMMC的bcl-2过表达可能有助于解释它们对化疗诱导凋亡的抗性。
