Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation.
Lack of apoptosis has been linked to prolonged survival of malignant B cells expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2 protein expressed along normal human B-cell maturation and to establish the frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2 expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144 patients was found to be aberrant in 66% of the cases, usually corresponding to bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT lymphoma were the only diagnostic groups constantly showing overexpression of bcl-2. Bcl-2 overexpression was also frequently found in precursor B-acute lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma, Burkitt lymphoma and multiple myeloma.
Menendez
P
P
Servicio General de Citometría, Universidad de Salamanca, Salamanca, Spain.
Vargas
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A
Bueno
C
C
Barrena
S
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Almeida
J
J
De Santiago
M
M
López
A
A
Roa
S
S
San Miguel
J F
JF
Orfao
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D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism*; D001853:Bone Marrow; D016022:Case-Control Studies; D002454:Cell Differentiation; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013154:Spleen
D019253:Proto-Oncogene Proteins c-bcl-2