Proviral integration of an Abelson-murine leukemia virus deregulates BKLF-expression in the hypermutating pre-B cell...

The transcription factor BKLF (basic Krüppel-like factor, KLF3) is a member of the Krüppel-like factors (KLF) family. KLF members harbor a characteristic C-terminal zinc-finger DNA-binding domain and bind preferentially to CACCC-motifs. BKLF is highly expressed in haematopoietic and erythoid cells and works either as repressor or activator of transcription in various genes. BKLF-deficient mice display myeloproliferative disorders and abnormalities in haematopoiesis. Other members of the KLF-family such as GKLF and BCL11A have been implicated in tumorigenesis, however, for BKLF such association has not yet been demonstrated. We report here that a single Abelson-murine leukemia virus (A-MuLV) provirus is present in the genome of the hypermutating murine pre-B cell line 18-81. The provirus has integrated into the locus of the transcription factor BKLF. In contrast to other A-MuLV transformed pre-B cell lines, BKLF is highly transcribed in cell line 18-81. BKLF transcripts originate from the retroviral long terminal repeats (LTRs) and BKLF protein can be detected by gel shift retardation assay. We hypothesize on a potential role of BKLF deregulation in tumorigenesis and/or in the induction of somatic hypermutation in cell line 18-81.