SUPPRESSION OF CELL-PROLIFERATION AND THE EXPRESSION OF A BCR-ABL FUSION GENE AND APOPTOTIC CELL-DEATH IN A NEW HUMAN CHRONIC MYELOGENOUS LEUKEMIA-CELL LINE, KT-1, BY INTERFERON-ALPHA

A new human leukemia cell line, KT-1, was established from a patient i n the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidas e and two Philadelphia chromosomes (Ph-1) [t(9;22)(q34;q11)] and lacke d normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/a bl-2 splice junction. When the KT-1 cells were cultured with interfero n (IFN)-alpha or IFN-gamma, the growth of the cells were dose-dependen tly suppressed. IFN-alpha and IFN-gamma exerted synergistic suppressiv e effects on the growth of KT-1 cells. Furthermore, IFN-alpha suppress ed the expression of the bcr-abl fusion gene in KT-1 cells, and induce d G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line sh ould be a valuable tool for studying the molecular mechanism of the su ppression of Ph-1 clone cells from CML by IFN. (C) 1998 by The America n Society of Hematology.