Ozawa Yukiyasu, Williams Ann H, Estes Myka L, Matsushita Norimasa, Boschelli Frank, Jove Richard, List Alan F
Experimental Therapeutics, H. Lee Moffitt Cancer & Research Institute, Tampa, FL 33612, United States.
Leuk Res. 2008 Jun;32(6):893-903. doi: 10.1016/j.leukres.2007.11.032. Epub 2008 Jan 7.
We investigated the role of Src family kinases (SFKs) in the regulation of STAT activation in myeloid leukemia cells. Two of 6 AML cell lines displayed constitutive STAT5 activation, whereas four cell lines had constitutive SFK activity. Treatment with the SFK inhibitors suppressed STAT5 activation and decreased viability. Akt phosphorylation and Mcl-1 expression decreased after SFK inhibition accompanied by apoptosis induction. In primary AML specimens, SFK inhibitors suppressed proliferation in 5 of 14 specimens. These data indicate that Src-STAT5 and Src-Akt pathways are integral survival signal pathways in AML cells. Src inhibition may represent a novel treatment strategy for investigation in AML.
我们研究了Src家族激酶（SFKs）在髓系白血病细胞中STAT激活调控中的作用。6个急性髓系白血病（AML）细胞系中有2个表现出组成型STAT5激活，而4个细胞系具有组成型SFK活性。用SFK抑制剂处理可抑制STAT5激活并降低细胞活力。SFK抑制后，Akt磷酸化和Mcl-1表达降低，并伴有凋亡诱导。在原发性AML标本中，SFK抑制剂在14个标本中的5个中抑制了增殖。这些数据表明，Src-STAT5和Src-Akt途径是AML细胞中不可或缺的生存信号途径。抑制Src可能代表一种用于AML研究的新治疗策略。
