Expression of Bcl-2 family of proteins in fresh myeloma cells

Abstract

Members of the

Suppression of apoptosis: role in cell growth and neoplasia

“…81 The importance of the Bcl-2 family of proteins is underscored by reports of their dysregulation in many hematological malignancies that can contribute to the resistance of such malignancies to pro-apoptotic chemotherapeutic drugs. [82][83][84][85][86][87][88][89][90] Apoptosis due to the cell receiving an abnormal proliferative signal…”

Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family

“…29 In large B-cell non-Hodgkin's lymphoma, multiple myeloma, or anaplastic large cell lymphoma (ALCL), overexpression of Bcl-2, or an increased number of Bcl-2-positive cells, correlated with poor prognosis. [36][37][38][39] Additionally, numerous studies have demonstrated Bcl-2 overexpression, and a correlation with poor prognosis, in nonhematological cancers, such as melanoma, [40][41][42] breast cancer, [43][44][45][46] prostate cancer, [47][48][49] small cell lung cancer (SCLC), 50,51 colorectal carcinoma, 52,53 bladder transitional cell carcinoma, [54][55][56][57] and solitary fibrous tumors. 58 Bcl-X L has also been implicated in the pathogenesis of several types of cancer.…”

“…61 Advanced and relapsed cases of multiple myeloma are characterized by high levels of Bcl-X L ; 61 earlier stages of the disease manifest higher levels of Bcl-2. 38 In nonhematological cancers, elevated levels of Bcl-X L were detected in bladder transitional cell carcinoma, 62 and squamous cell cancer of the oropharynx, and correlated with poor remission after radiotherapy. 63 Both Bcl-X L and Bcl-2 are expressed in breast cancers.…”

“…106 These effects are mimicked in Bcl-X L -overexpressing hematological malignancies such as AML 59 and multiple myeloma. 38,61 Bcl-X L has been reported to participate in Bcr-Abl-mediated drug resistance, since Bcl-X L antisense oligonucleotide increased the susceptibility of Bcr-Abl-HL-60 cells to staurosporine. 107 Treatment of cell lines representing human prostate cancer, 108 bladder cancer, 109 colon cancer, 110 hepatoma, 111 gastric cancer, 112 and pancreatic carcinoma 113 with Bcl-X L antisense sensitized these cells to apoptosis.…”

G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma

“…Bcl-2 is expressed in myeloma cell lines and in myeloma patients' samples despite the absence of molecular evidence of Bcl-2 rearrangements. [16][17][18][19][20][21][22] Bcl-2 inhibits apoptosis by forming inactivating heterodimers with proapoptotic Bcl-2 family proteins, and by preventing the collapse of the mitochondrial transmembrane potential, the release of cytochrome c and Smac/DIABLO from mitochondria into the cytosol, and the activation of caspases. [23][24][25][26] Overexpression of Bcl-2 in transgenic mice prolongs the lifespan of plasma cells and in combination with abnormal expression of other oncogenes such as c-Myc, contributes to the development of immature pre-B-cell lymphoma, large-cell lymphoma or plasmacytoma in 40-60% of the mice.…”