A T(6-12)(Q23-P13) RESULTS IN THE FUSION OF ETV6 TO A NOVEL GENE, STL, IN A B-CELL ALL CELL-LINE

ETV6 (TEL) is rearranged in various types of hematologic malignancies. The B-cell precursor acute lymphoblastic leukemia (ALL) cell line SUP -BZ has a t(6;12)(q23;p13) involving ETV6 at 12p13 and a submicroscopi c deletion of the other ETV6 allele, The reciprocal translocation resu lts in the fusion of ETV6 to a previously unknown gene at 6q23, which we named STL (six-twelve leukemia gene). Both reciprocal fusion transc ripts can be detected: On the der (6) chromosome, the ETV6/STL mRNA sh ows an apparently out of frame fusion of ETV6 at nucleotide 187 to STL , which would result in the addition of 14 amino acids to the first 54 amino acids of ETV6. On the der (12) chromosome three different varia nts of the STL/ETV6 fusion mRNA could be detected; variable size segme nts were inserted at the breakpoint between STL and ETV6 exon 3. One o f these variants could give rise to a protein in which the first 54 am ino acids of ETV6 are replaced by 12 amino acids from one of the STL s hort open reading frames. Sequence analysis of a 1.4 kb STL cDNA clone from a skeletal muscle library revealed no long open reading frames. This cell line will be very useful in studying the different mechanism s by which alterations of ETV6 contribute to leukemogenesis and in tes ting the hypothesis that ETV6 might act as a tumor suppressor gene. (C ) 1997 Wiley-Liss, Inc.