NONRANDOM CYTOGENETIC CHANGES ACCOMPANY MALIGNANT PROGRESSION IN CLONAL LINES OF ABELSON VIRUS-INFECTED LYMPHOCYTES

Initially, lymphoid cells transformed by v-abl or BCR/ABL oncogenes ar e poorly oncogenic but progress to full transformation over time. Alth ough expression of the oncogene is necessary to initiate and maintain transformation, other molecular mechanisms are thought to be required for full transformation. To determine whether tumor progression in ABL oncogene-transformed lymphoid cells has a genetic basis, we examined whether progression of the malignant phenotype of transformed clones c orrelates with particular cytogenetic abnormalities, A modified in vit ro bone marrow transformation model was used to obtain clonal Abelson murine leukemia virus-transformed B lymphoid cells that were poorly on cogenic, Multiple subclones were then derived from each clone and main tained over a marrow-derived stromal cell line for several weeks. Over time, clonally related Abelson murine leukemia virus-transformed subc lones progressed asynchronously to full transformation. The data show that tumor progression can occur in the absence of detectable cytogene tic changes but, more importantly, that certain cytogenetic abnormalit ies appear reproducibly in highly malignant subclones. Therefore, thre e independent subclones showed deletion in a common region of chromoso me 13. Other highly malignant cells carried a common breakpoint in the X chromosome, and, finally, two subclones carried an additional chrom osome 5. These results are consistent with the hypothesis that ABL onc ogenes are sufficient for the initial transformation of cells but that additional genetic events can drive oncogenic progression. These obse rvations further suggest that diverse genetic mechanisms may be able t o drive tumor progression in cells transformed with ABL oncogenes. (C) 1994 by The American Society of Hematology.