Kawauchi Kiyotaka, Ogasawara Toshie, Yasuyama Masako
Department of Medicine, Tokyo Women's Medical University Daini Hospital, Japan.
Int J Hematol. 2002 Jun;75(5):508-13. doi: 10.1007/BF02982115.
B-cell chronic lymphocytic leukemia (B-CLL) cells express on their surface membranes immunoglobulin (Ig) M or IgD, both of which normally function as B-cell antigen receptors (BCRs). However, in contrast to normal B-cells, in B-CLL cells several important signaling pathways, such as the activation of protein tyrosine kinase via BCR, are defective. We have examined whether the activities of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38 MAPK, and Akt kinase, are functional in B-CLL cells, because these kinases play critical roles in activation in response to BCR stimulation, tumor cell growth, and survival. In B-CLL cells, BCR cross-linking neither induced activation nor enhanced the activities of Lyn, Syk, p21ras, JNK, p38 MAPK, or Akt kinases, whereas p38 MAPK and Akt were constitutively active. In contrast, BCR cross-linking resulted in ERK activation, although the activation in quiescent cells was case dependent. These results suggest that some signaling pathways, such as the activation of ERK through BCR, are functional in B-CLL cells despite the extensive impairment of signaling pathways.
B细胞慢性淋巴细胞白血病（B-CLL）细胞在其表面膜上表达免疫球蛋白（Ig）M或IgD，这两种蛋白通常作为B细胞抗原受体（BCR）发挥作用。然而，与正常B细胞不同，在B-CLL细胞中，一些重要的信号通路存在缺陷，比如通过BCR激活蛋白酪氨酸激酶。我们研究了丝裂原活化蛋白激酶（MAPK）的活性在B-CLL细胞中是否发挥作用，这些激酶包括细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）、p38 MAPK和Akt激酶，因为这些激酶在响应BCR刺激的激活、肿瘤细胞生长和存活中起关键作用。在B-CLL细胞中，BCR交联既不诱导Lyn、Syk、p21ras、JNK、p38 MAPK或Akt激酶的激活，也不增强其活性，而p38 MAPK和Akt呈组成性激活。相比之下，BCR交联导致ERK激活，尽管在静止细胞中的激活情况取决于具体情形。这些结果表明，尽管信号通路存在广泛损伤，但一些信号通路，如通过BCR激活ERK，在B-CLL细胞中仍发挥作用。
