Tortora G, Tagliaferri P, Clair T, Colamonici O, Neckers L M, Robins R K, Cho-Chung Y S
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892.
Blood. 1988 Jan;71(1):230-3.
Cyclic AMP (cAMP)-dependent protein kinase may play a role in the functional and morphological differentiation of leukemic cells. In this study, we showed that the cAMP analogs, potent activators of protein kinase recently shown to be selective for either site 1 or site 2 cAMP binding sites of protein kinase, demonstrate potent growth inhibition of acute promyelocytic, chronic myelocytic, and acute lymphocytic leukemic cell lines with no sign of toxicity. The growth inhibition accompanied monocytic differentiation in HL-60 cells and a loss of nuclear terminal deoxynucleotidyl transferase activity in Molt-4 leukemic cells. The growth inhibition also paralleled a decrease in c-myc protein and RI cAMP receptor protein. Thus, cAMP analogs selective for either site 1 or site 2 of the protein kinase appear to restore a coupling of proliferation and maturation in leukemic cells.
环磷酸腺苷（cAMP）依赖性蛋白激酶可能在白血病细胞的功能和形态分化中起作用。在本研究中，我们表明，cAMP类似物是蛋白激酶的强效激活剂，最近显示其对蛋白激酶的位点1或位点2的cAMP结合位点具有选择性，可对急性早幼粒细胞、慢性粒细胞和急性淋巴细胞白血病细胞系表现出强效生长抑制作用，且无毒性迹象。在HL-60细胞中，生长抑制伴随着单核细胞分化，而在Molt-4白血病细胞中，生长抑制伴随着核末端脱氧核苷酸转移酶活性的丧失。生长抑制还与c-myc蛋白和RI cAMP受体蛋白的减少同时出现。因此，对蛋白激酶位点1或位点2具有选择性的cAMP类似物似乎可恢复白血病细胞增殖与成熟的偶联。
