Stacchini A, Fubini L, Severino A, Sanavio F, Aglietta M, Piacibello W
Department of Biomedical Sciences and Human Oncology, Medical School of Torino, University of Turin, Italy.
Leukemia. 1996 Oct;10(10):1584-91.
The stem cell tyrosine kinase 1 (STK1) protein is the human homologue of the murine FLT3 gene product, a receptor belonging to the FMS/KIT family. FLT3 and KIT with their ligands control the growth and differentiation of early human hemopoietic cells. In the present study, 16 cases of acute myeloid leukemia (AML) were examined by flow cytometry for cell surface expression of FLT3 and KIT receptors. All cases were also tested for their proliferative response to human FLT3 ligand (FL) and KIT ligand (KL) and for colony formation in the presence of single or associated cytokines. Among 16 AML cases tested, 10/16 expressed FLT3 receptor and 12/16 expressed KIT receptor, without any correlation with FAB subtype. FL and KL stimulated the proliferation of leukemic blasts in 11/16 AML cases (including five FLT3 or KIT receptor-negative cases), with an additive effect when added simultaneously. By contrast, some receptor-expressing AMLs did not display significant proliferative responses to their respective ligands. FL and KL as single factors induced or significantly increased the colony formation by clonogenic precursor cells respectively in eight and six of 13 cases tested. In some cases growth factor association significantly enhanced colony growth. Taken together these observations provide evidence that the pattern of FLT3 and KIT receptor expression is extremely variable among the AMLs and that receptor presence is not necessarily combined with proliferative and clonogenic response or vice versa.
干细胞酪氨酸激酶1（STK1）蛋白是小鼠FLT3基因产物的人类同源物，FLT3基因产物是一种属于FMS/KIT家族的受体。FLT3和KIT与其配体共同控制早期人类造血细胞的生长和分化。在本研究中，通过流式细胞术检测了16例急性髓系白血病（AML）患者细胞表面FLT3和KIT受体的表达情况。所有病例还检测了其对人FLT3配体（FL）和KIT配体（KL）的增殖反应以及在单一或联合细胞因子存在下的集落形成情况。在检测的16例AML病例中，10/16表达FLT3受体，12/16表达KIT受体，与FAB亚型无任何相关性。FL和KL刺激了11/16例AML病例（包括5例FLT3或KIT受体阴性病例）白血病原始细胞的增殖，同时添加时具有相加作用。相比之下，一些表达受体的AML对其各自配体未显示出明显的增殖反应。在13例检测病例中，FL和KL作为单一因子分别在8例和6例中诱导或显著增加了克隆形成前体细胞的集落形成。在某些情况下，生长因子联合使用显著增强了集落生长。综上所述，这些观察结果表明，FLT3和KIT受体的表达模式在AML中变化极大，受体的存在不一定与增殖和克隆形成反应相关，反之亦然。
