Twenty-nine cases of non-Hodgkin's lymphoma of low-grade malignancy in a European population were investigated for the presence of bcl-2 and bcl-1 gene rearrangement.
Southern blotting was used to detect rearrangement of the bcl-2 gene in 104 cases of non-Hodgkin's lymphoma subclassified by the Working Formulation, 24 cases of B cell chronic lymphocytic leukemia (B-CLL) and 14 cases of T cell malignancy.
Forced expression of bcl-2 also attenuated TNF alpha-mediated cytotoxicity of glioma cell lines in the presence of actinomycin D and cycloheximide and conferred partial protection from irradiation and the cancer chemotherapy drugs, cisplatin and BCNU.
Genotypic selection of oncogenic mutations at the BCL2 and p53 loci has revealed that the cell specificity of oncogenic mutations in persons without cancer correlates well with sites of tumor origin, indicating that cells bearing such mutations are the likely precursors of future tumors.
The findings thus contribute to the mapping of functional domains in Bcl-2 proteins, and raise the possibility that the EBV-encoded p19-BHRF-1 protein may be able to substitute for p26-Bcl-2 in the development of some types of cancer.
Interestingly these fragile sites were located in the same chromosomal bands as the oncogenes, MOS, MYC, BCL-1 and BCL-2 as well as cancer breakpoints specifically associated with non-Hodgkin's lymphoma, suggesting the possibility that fragile sites may play a critical role in the pathogenesis of non-Hodgkin's lymphoma.
Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
In this review, the regulation of PCD by members of the bcl-2 family of proteins is discussed, primarily within the context of human cancers where abnormalities in the expression of BCL2 family genes frequently occur and contribute both to the origins of cancer and our difficulty in treating it.
Future investigations in apoptosis probably will provide further insight into the cell-signaling cascades regulating apoptosis, the mechanism(s) by which Bcl-2 inhibits apoptosis, and the precise role of apoptosis in cancer initiation, promotion, and progression.
Overproduction of the Bcl-2 protein also prevents cell death induced by nearly all cytotoxic anticancer drugs and radiation, thus contributing to treatment failures in patients with some types of cancer.
In this review we mainly discuss bcl-2 and its partners in human cancers and how their disregulation might contribute to the development and the difficult treatment of cancer.
A role for altered programmed cell death in cancer stems from the description of alterations on tumor-associated genes involved in the regulation of apoptosis such as p53 and bcl-2.
Five putative drug resistance parameters (MDR1/P-glycoprotein, MDR-associated protein, glutathione-S-transferase, bcl-2 and topoisomerase IIalpha) in 57 newly diagnosed acute myeloid leukaemias. Swiss Group for Clinical Cancer Research (SAKK).
Among the adult patients, a favorable prognostic indicator was low-tumor grade (P = 0.05). bcl-2-positive tumors occurred with similar frequencies in WHO grades III and IV of malignancy.
In this review article we describe the role of the bcl-2/ced-9 gene family in cancer and discuss the general implications of defects in the apoptosis program for tumourigenesis and resistance of cancer cells to chemotherapy in light of current knowledge of the molecular mechanisms of cell death.
Information about the biochemical mechanisms of action of the Bcl-2 protein and other members of the Bcl-2 family is beginning to suggest strategies for overcoming the cytoprotective effects of Bcl-2 overexpression in lymphomas, leukemias, and other types of cancer.