Wickremasinghe R G, Piga A, Mire A R, Taheri M R, Yaxley J C, Hoffbrand A V
Leuk Res. 1985;9(12):1443-50. doi: 10.1016/0145-2126(85)90034-7.
We have quantitated tyrosine protein kinase (TPK) activity in particulate and cytosolic fractions from human leukemic cells. Slowly proliferating cells from patients with chronic lymphocytic leukemia (CLL) had levels of TPK similar to those of quiescent normal lymphocytes. Cells from patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and chronic granulocytic leukemia (CGL) contained markedly lower levels of TPK activity, similar to the levels in phytohaemagglutinin-stimulated (proliferating) normal lymphocytes and in bone marrow cells. This suggested that TPK is part of a mechanism for transducing growth signals and is down-regulated following signal transmission. We also identified endogenous substrates for TPK in leukemic cells. Particulate fractions from ALL, CLL and AML cells contained substrates identical to those previously detected in normal lymphocytes. In particular, a 38kD substrate thought to be involved in early stages of growth signal transduction in normal lymphocytes was found in all samples of these groups examined. Cytosolic fractions from these groups of leukemia cells contained higher molecular weight substrates not found in resting or proliferating normal lymphocytes or bone marrow cells. In contrast, TPK substrates in both particulate and cytosolic fractions from CGL cells resembled those of normal bone marrow cells in that only proteins with molecular weight below 40kD were labelled on tyrosine. We conclude that leukemic cells do not contain higher levels of TPK than do normal hemopoietic cells. Qualitative differences in TPK species or in their substrates may result in aberrant regulation of proliferation in leukemic cells. However, we cannot exclude the possibility that additional TPK substrates detected in leukemic cells were a feature of the normal equivalent hematopoietic cells from which the leukemia cells were derived.
我们已经对人白血病细胞微粒体和胞质组分中的酪氨酸蛋白激酶（TPK）活性进行了定量分析。慢性淋巴细胞白血病（CLL）患者的缓慢增殖细胞中TPK水平与静止正常淋巴细胞中的水平相似。急性淋巴细胞白血病（ALL）、急性髓细胞白血病（AML）和慢性粒细胞白血病（CGL）患者的细胞中TPK活性水平明显较低，类似于植物血凝素刺激（增殖）的正常淋巴细胞和骨髓细胞中的水平。这表明TPK是转导生长信号机制的一部分，并且在信号传递后被下调。我们还在白血病细胞中鉴定了TPK的内源性底物。ALL、CLL和AML细胞的微粒体组分含有与先前在正常淋巴细胞中检测到的底物相同的底物。特别是，在这些组的所有检测样本中都发现了一种38kD的底物，该底物被认为参与正常淋巴细胞生长信号转导的早期阶段。这些白血病细胞组的胞质组分含有在静止或增殖的正常淋巴细胞或骨髓细胞中未发现的分子量更高的底物。相比之下，CGL细胞微粒体和胞质组分中的TPK底物与正常骨髓细胞的底物相似，因为只有分子量低于40kD的蛋白质在酪氨酸上被标记。我们得出结论，白血病细胞中的TPK水平并不高于正常造血细胞。TPK种类或其底物的质的差异可能导致白血病细胞增殖的异常调节。然而，我们不能排除在白血病细胞中检测到的额外TPK底物是白血病细胞所源自的正常等效造血细胞的特征的可能性。
