Taguchi T, Kiyokawa N, Sato N, Saito M, Fujimoto J
Department of Pathology, National Children's Medical Research Center, Tokyo, Japan.
Exp Hematol. 2000 Jan;28(1):55-64. doi: 10.1016/s0301-472x(99)00127-7.
To identify molecules involved in signaling for early B-cell development, we investigated the expression of signal transduction-related proteins in B-cell progenitors.
[corrected] Normal as well as leukemic B-cell progenitors were examined by immunoblotting and immunofluorescence study.
[corrected] 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. [corrected] 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. [corrected] 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.
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.
为了鉴定参与早期B细胞发育信号传导的分子,我们研究了B细胞祖细胞中信号转导相关蛋白的表达情况。
[已校正] 通过免疫印迹和免疫荧光研究对正常以及白血病B细胞祖细胞进行检测。
[已校正] 在对多种信号转导分子表达情况的调查中,发现Src家族蛋白酪氨酸激酶在早期B细胞分化过程中存在差异表达。[已校正] 对新鲜制备的前体B细胞急性淋巴细胞白血病细胞和B系细胞系的分析表明,Hck和Lyn是这类白血病母细胞中表达的主要Src家族蛋白酪氨酸激酶。[已校正] 然而,在这些细胞中发现了Hck和Lyn表达的异质性,随后根据Hck和Lyn的表达模式将前体B细胞急性淋巴细胞白血病细胞分为Hck/Lyn双阴性、Hck占主导、Hck/Lyn双阳性和Lyn占主导四类。对正常B系细胞的进一步研究表明,Src家族蛋白酪氨酸激酶在B细胞个体发育过程中以分化依赖的方式顺序表达,并且Hck的主要表达是B细胞祖细胞的共同特征,而Lyn的表达在成熟B细胞中更为显著。
尽管生物学意义尚不清楚,但Src家族蛋白酪氨酸激酶的顺序表达在早期B细胞分化的调控中应发挥作用。