Presence of P210bcrabl is associated with decreased expression of a beta chemokine C10 gene in a P210bcrabl-positive myeloid leukemia cell fine

Background: Chronic myelogenous leukemia (CML) is thought to start with the acquisition of the t(9;22) chromosomal translocation that codes for the P2 10bcrabl tyrosine-specific protein kinase. The CML cells exhibit anchorage- independent cell growth and genetic instability. After the initial phase, t he cells acquire the phenotype of growth factor-independent growth. After t he chronic phase, the disease evolves into the accelerated and blastic phas es through the process of sequential random mutation. Materials acid Methods: To identify some of the genetic changes that contri bute to the phenotype of blastic and accelerated phase cells, we used diffe rential display PCR to compare levels of cDNA reverse transcripts of mRNA i n 32Dc13 cells and 32Dc13 cells that were stably transfected with a bcrabl cDNA plasmid in a constitutively expressed transcription unit. These cells were designated 32Dc13P210bcrabl. For these studies, we used the 32D myeloi d leukemia cell line, which depends on IL-3 for growth. Results: Following introduction of the bcr-abl cDNA through transfection, t he cell line became growth factor independent, mimicking the change in phen otype that occurs during the later phases of CML. These differential displa y screening assays detected altered levels of transcripts for 28 genes. Of interest to the biology of growth factor-independent growth in the bcrabl-p ositive 32D cells was the fact that the C10 beta chemokine gene was express ed at higher levels in the 32Dc13 cells than in the 32Dc13P210bcrabl cells. Conclusions: These studies show that a C10 beta chemokine gene was expresse d at different levels with or without P210bcrabl.