The nature of the B lymphocyte in B-chronic lymphocytic leukemia.
We have analyzed phenotypic, functional, and molecular properties of B-chronic lymphocytic leukemia (B-CLL) cells as compared to normal B cell differentiation stages and/or subsets. The possibility that the target B cell population transformed by the I primary oncogenic event(s) belongs to the normal CD5+ B cell subset from B mantle zone of secondary follicles is highly likely on phenotypic grounds. Though the genes responsible for the primary oncogenic event are presently unknown, a number of functional and molecular findings indicate that the end-product of their transforming activity is a cell frozen in the G0 phase of the cell cycle. This cell has several abnormalities that prevent an appropriate mitogenic response and presents a pattern of apoptosis-related gene expression that hinders apoptotic death. Pivotal to this apoptosis-escaping capacity is the expression of Bcl-2. We suggest that the increased expression of Bcl-2 together with an asynchronism between the expression of Bcl-2, c-myc, and APO1/Fas gene products shift the cellular balance away from apoptosis thereby helping the progressive accumulation in G0 of malignant CD5+ B cells.
Caligaris-Cappio
F
F
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Gottardi
D
D
Alfarano
A
A
Stacchini
A
A
Gregoretti
M G
MG
Ghia
P
P
Bertero
M T
MT
Novarino
A
A
Bergui
L
L
D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor
D015703:Antigens, CD; D000954:Antigens, Surface; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D011505:Protein-Tyrosine Kinases