The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case

The PAX5 gene, encoding the B-cell-specific activator protein, is a critica l determinant of commitment to the B-lymphocyte pathway. This gene, mapped at 9p13, is juxtaposed to the immunoglobulin heavy chain (IgH) gene as a re sult of the t(9;14)(p13;q32), a rare but recurring translocation found in a subset of B-cell non-Hodgkin's lymphoma cases. In all of these, this trans location results in deregulated expression of the gene product because of t he proximity of IgH, We present here the molecular characterization of a pr eviously reported acute lymphoblastic leukemia case carrying a t(9;12)(q11; p13) translocation, Using 5 ' rapid amplification of cDNA ends PCR, a novel chimeric transcript was identified that contained the NH2-terminal region of PAX5 and most of the ETV6/TEL gene on 12p13, According to the fusion tra nscript, the resulting chimeric protein would retain the PAX5 paired-box do main and both the helix-loop-helix and DNA binding domains of TEL, Thus, it is reasonable to hypothesize that this protein could act as an aberrant tr anscription factor. This is the first report of PAX5 rearrangement in a hum an malignancy resulting in a chimeric transcript.