The leukaemic cells of more than 90% of chronic myelogenous leukaemia (CML) patients and of 10% of acute lymphocytic leukaemia (ALL) patients carry the t(9:22) (q34:q11) translocation which generates the Philadelphia chromosome (Ph1). In CML the abl gene is translocated from chromosome 9 to the centre of the bcr gene on chromosome 22 and this results in production of chimaeric bcr-abl RNA translated into a protein of relative molecular mass (Mr) 210,000 (210K). Our data indicate that in ALL abl is translocated into the 5' region of the bcr gene. The consequence of this is the expression of a fused transcript in which the first exon of bcr is linked to the second abl exon. This transcript encodes a 190K protein kinase.

The activation of the cellular oncogene c-mos in mouse plasmacytoma XRPC24 was found to result from the insertion of a 4.7-kilobase-pair cellular DNA element, within the cmos coding region. The element terminates on both sides with a direct repeat of around 335 nucleotides. The repeat as well as internal sequences of the element show strong homology to endogenous intracisternal A-particle (LAP) genes. The LAP genome integrated within c-mos in a headto-head (5' to 5') configuration. This juxtapositioned the LAP 5' long terminal repeat next to the bulk of the oncogene's coding region and shifted c-mos 5' coding and flanking sequences to a position further upstream. The significance of several aspects of this activation and transposition event is discussed.c-mos is a member of the family of cellular sequences, termed onc genes, which possess the potential to become malignant through incorporation into the genome of retroviruses (1) or by undergoing alterations within the cell (2). c-nos is the progenitor of the transforming information (v-mos) in Moloney murine sarcoma virus. The virus is presumably a recombinant between Moloney murine leukemia virus and the c-nos gene of BALB/ c mice (3, 4). c-and v-mos are composed of nearly identical sequences over their coding region, with the exception that cmos contains 21 additional codons at the 5' terminus, substituted in v-mos with 5 codons derived from viral helper sequences (5, 6). A Mr 37,000 protein identified within virus-infected cells (7) is encoded by the 374 codons of v-mos and presumably triggers cellular malignant transformation. No homologous protein coded by c-mos has been detected in normal cells.In a recent study (8) we described the rearrangement of the c-mos gene in mouse plasmacytoma XRPC24. Sequences from the 5' region of the gene, including 264 nucleotides of the presumed mos coding sequence as well as 5' flanking DNA, were substituted with a unique DNA. This rearrangement was accompanied by the appearance of mos transcripts in the tumor. Moreover, the molecularly cloned rearranged gene (termed rcmos), unlike its normal counterpart, induced transformed foci upon transfection into NIH/3T3 monolayers.More recently it was shown (9) that a 0.35-kilobase-pair (kbp) segment of the unique DNA, immediately adjacent to the junction point with c-mos sequences retained in rc-mos, had 88% sequence homology with the long terminal repeat (LTR) of an endogenous genetic element molecularly cloned from a library of mouse DNA (10). This element is a member of a family of highly reiterated endogenous mouse genes [intracisternal A particle (IAP) genes] homologous to the RNA of IAPs. The latter are noninfectious retrovirus-like structures found regularly in early mouse embryos (11-13) and present abundantly in every mouse plasmacytoma (14) and other mouse tumors (15).The association between an IAP LTR and the rearranged cellular mos was of considerable interest because it constituted one example of activation of a cellular oncogene by a mechanism involving relocat...

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The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes. Using a sensitive RNase protection technique, we analyzed mRNA from a large number of CML patients. In most, we identified one or both species of bcr-abl chimeric transcripts. These two mRNAs vary in the specific bcr exon joined to abl exon II and are translated into slightly different proteins. The amounts of the fused mRNA within leukemia cells vary considerably between individuals and do not correlate with the phase of the disease.