Presence of P2lObcrabl Is Associated with Decreased Expression of a Beta Chemokine CIO Gene in a P210bcrabl-Positive Myeloid Leukemia Cell Line

Background: Chronic myelogenous leukemia (CML) is thought to start with the acquisition of the t(9;22) chromosomal translocation that codes for the P2 lObcrabl ty-rosine-specific protein kinase. The CML cells exhibit an-chorage-independent cell growth and genetic instability. After the initial phase, the cells acquire the phenotype of growth factor-independent growth. After the chronic phase, the disease evolves into the accelerated and blastic phases through the process of sequential random muta-tion. Materials and Methods: To identify some of the genetic changes that contribute to the phenotype of blastic and accelerated phase cells, we used differential display PCR to compare levels of cDNA reverse transcripts of mRNA in 32Dc13 cells and 32Dc13 cells that were stably transfected with a bcrabl cDNA plasmid in a constitu-tively expressed transcription unit. These cells were des-ignated 32Dc13P210bcrabl. For these studies, we used the 32D myeloid leukemia cell line, which depends on IL-3 for growth. Results: Following introduction of the bcr-abl cDNA through transfection, the cell line became growth factor independent, mimicking the change in phenotype that occurs during the later phases of CML. These differential display screening assays detected altered levels of transcripts for 28 genes. Of interest to the biology of growth factor-independent growth in the bcrabl-positive 32D cells was the fact that the C10 c3 chemokine gene was expressed at higher levels in the 32Dc1 3 cells than in the 32Dc1 3P2 lObcrabl cells. Conclusions: These studies show that a C10IO chemokine gene was expressed at different levels with or without P2 I Obcrabl.