Cells of most tissues require adhesion to a surface to grow. However, for hematopoietic cells, both stimulation and inhibition of proliferation by adhesion to extracellular matrix components have been described. Furthermore, it has been suggested that progenitor cells from chronic myelogenous leukemia show decreased  1 integrin-mediated adhesion to fibronectin, resulting in increased proliferation and abnormal trafficking. However, we show here that the chronic myelogenous leukemia-specific fusion protein p210bcr͞abl stimulates the expression of ␣ 5  1 integrins and induces adhesion to fibronectin when expressed in the myeloid cell line 32D. Moreover, proliferation of both p210bcr͞abl-transfected 32D (32Dp210) cells and untransfected 32D cells is stimulated by immobilized fibronectin. Cell cycle analysis revealed that nonadherent 32D and 32Dp210 cells are arrested in late G 1 or early S phase, whereas the adherent fractions continue cycling. Although both adherent and nonadherent p210bcr͞abl-transfected and parental 32D cells express equal amounts of cyclin A, a protein necessary for cell cycle progression at the G 1 ͞S boundary, cyclin A complexes immunoprecipitated from 32D cells cultured on immobilized fibronectin were found to be catalytically inactive in nonadherent but not in adherent cells. In addition, as compared with untransfected 32D cells, cyclin A immunoprecipitates from 32Dp210 cells exhibited a greatly elevated kinase activity and remained partially active irrespective of the adhesion status. The lack of cyclin A͞cyclin-dependent kinase (CDK) 2 activity in nonadherent 32D cells appeared to result from increased expression and cyclin A complex formation of the CDK inhibitor p27 Kip1 . Taken together, our results indicate that adhesion stimulates cell cycle progression of hematopoietic cells by downregulation of p27 Kip1 , resulting in activation of cyclin A͞CDK2 complexes and subsequent transition through the G 1 ͞S adhesion checkpoint.