BIOLOGICAL PROPERTIES AND GROWTH IN SCID MICE OF A NEW MYELOGENOUS LEUKEMIA-CELL LINE (KBM-5) DERIVED FROM CHRONIC MYELOGENOUS LEUKEMIA-CELLS IN THE BLASTIC PHASE

The establishment and the biological properties of a new leukemic cell line (KBM-5) derived from a patient in the blastic phase of chronic m yelogenous leukemia are described. The cells exhibited multiple copies of the Philadelphia chromosome, and a high level of p210Bcr-Abl kinas e activity was detected with rabbit anti-Abl and anti-Bcr (exon 3) pep tide antisera. Use of specific primers and polymerase chain reaction f ollowed by Southern blotting revealed that KBM-5 cells carried a bcr3- ABLII splice junction. While a normal BCR message was detected, no nor mal ABL message was found. The cells were phenotypically myeloid with monocytic differentiation. The high cloning efficiency in semisolid me dia was independent of the presence of exogenous colony-stimulating fa ctors. In vitro exposure to inducers of differentiation, such as retin oic acid, dimethyl sulfoxide, or hemin, failed to influence the growth rate of the cells and their level of differentiation. KBM-5 cells are highly resistant to the antiproliferative action of recombinant alpha - and gamma-interferons. Although sensitive to recombinant tumor necro sis factor alpha, they were completely resistant to natural killer cel l action. KBM-5 cells constitutively expressed mRNA for tumor necrosis factor alpha but not for gamma-interferon, other interleukins, or hem atopoietic growth factors. The KBM-5 cells that were transplanted into SCID mice manifested metastatic potential and tissue invasiveness sim ilar to the way leukemic cells in humans do. This new KBM-5 cell line represents a helpful model for examining in vitro and in vivo modulati on of the growth and properties of leukemic cells by using biological and chemotherapeutic agents.