ZAP-70 Expression in Pro, Pre, Mature B Cells

February 10, 2006

Clin Cancer Res. 2006 Feb 1;12(3):726-734.

ZAP-70 Expression in Normal Pro/Pre B Cells, Mature B Cells, and in B-

Cell Acute Lymphoblastic Leukemia.

Crespo M, Villamor N, Gine E, Muntanola A, Colomer D, Marafioti T,

M, Camos M, Campo E, Montserrat E, Bosch F.

Authors' Affiliations: Departments of Hematology and Hematopathology,

Institut d'Investigacions Biomediques August Pi i Sunyer, Hospital

Clinic, Barcelona, Spain; and Department of Clinical Laboratory

Sciences, Radcliffe Hospital, Oxford, United Kingdom.

PURPOSE: The ZAP-70 gene is normally expressed in T and natural

killer cells, where it is required for the T-cell receptor (TCR)

signaling. More recently, it has been described that ZAP-70

contributes to the B-cell development at early stages of B-cell

differentiation in mice. The purpose was to investigate the presence

of ZAP-70 in normal pro/pre B cells and mature B cells and in tumoral

cells from B-acute lymphoblastic leukemias (B-ALL).

EXPERIMENTAL DESIGN: ZAP-70 expression was ascertained by flow

cytometry, immunofluorescence, Western blot, and quantitative reverse

transcription-PCR. Analysis of ZAP-70 and other signaling proteins of

the pre-TCR/TCR was done by Western blot.

RESULTS: ZAP-70 was expressed in pro/pre B cells but not in normal

mature B cells derived from bone marrow, peripheral blood, or tonsil.

Among tumoral cells, ZAP-70 was expressed in 56% of B-ALLs with

pro/pre B-cell phenotype and in 4 of 6 Burkitt/ALL lymphomas. In B-

ALL cells, expression of CD38 protein correlated with ZAP-70

expression (P = 0.05). Mutational analysis of the ZAP-70 gene

revealed the absence of mutations in cases lacking ZAP-70 expression.

Moreover, other elements of the pre-TCR/TCR signaling pathway, like

LAT and Lck, were also found in B-ALL cells.

CONCLUSIONS: Among normal B-cell subsets, ZAP-70 was found expressed

in normal pro/pre B cells but not in a significant proportion of

normal B cells with mature phenotype. Moreover, the presence of ZAP-

70 in B-ALLs probably reflects their cellular origin. The lack of ZAP-

70 expression in normal mature B cells suggests that its expression

in mature-derived neoplasms with different cellular origin, such as

Burkitt's lymphoma and chronic lymphocytic leukemia, might be due to

an aberrant phenomenon.

PMID: 16467082 [PubMed - as supplied by publisher]

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