Abstract

Objective. To identify molecules involved in signaling for early B-cell development, we investigated the expression of signal transduction-related proteins in B-cell progenitors. Normal as well as leukemic B-cell progenitors were examined by immunoblotting and immunofluorescence study. In a survey of the expression of a broad range of signal transduction molecules, the Src-family protein tyrosine kinases were found to be differentially expressed in early B-cell differentiation. Materials and Methods. Analysis of freshly prepared precursor-B acute lymphoblastic leukemia cells and B-lineage cell lines showed Hck and Lyn are major Src-family protein tyrosine kinases expressed in this type of leukemic blasts. Results. However, heterogeneity of Hck and Lyn expression was found in these cells, and precursor-B acute lymphoblastic leukemia cells subsequently were classified according to the expression pattern of Hck and Lyn as Hck/Lyn dual-negative, Hck-predominant, Hck/Lyn dual-positive, and Lyn-predominant. Further studies on normal B-lineage cells indicated that the Src-family protein tyrosine kinases are expressed sequentially in a differentiation-dependent fashion during B-cell ontogeny and that the predominant expression of Hck is a common feature in B-cell progenitors, whereas Lyn expression is more significant in mature B cells. Conclusions. Although the biologic significance remains unknown, sequential expression of Src-family protein tyrosine kinases should play a role in regulation of early B-cell differentiation.

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