Reciprocal fusion transcripts and predicted fusion proteins from MLL-FRYL translocation. (A) MLL exon 7(10) sense and FRYL exon 53 antisense primers were used to amplify der(11) transcripts from randomly primed first-strand cDNA. FRYL exon 50 sense and MLL exon 10(13) antisense primers were used for the der(4) transcript. Products are shown in the gels on the left. Sequences of fusion transcripts obtained by direct sequencing or sequencing of subclones were compared with MLL (GenBank accession no. L04284) and FRYL (KIAA0826; GanBank accession no. NM_015030) cDNAs for exon designations (right). MLL exon/intron numbers are Rasio et al designations²⁴  with parenthetical Nilson et al designations²⁵  alongside. A vertical line has been inserted to indicate 2 distinct gels. (B) Schematics of reciprocal fusion proteins predicted from der(11) and der(4) fusion transcripts. Regions of MLL and FRYL are black and gray, respectively. Examples of predicted fusion proteins shown are those from 5′-MLL exon 8(11)-FRYL exon 51-3′ and 5′-FRYL exon 50-MLL exon 9(12)-3′ transcripts, which were not alternatively spliced, incompletely processed and did not contain FRYL exon duplications. Predicted amino acid sequences of the fusion proteins were analyzed using SMART (Simple Modular Architecture Research Tool; http://smart.embl-heidelberg.de/). The amino acids from PHD 1 of MLL retained in the predicted N-MLL-FRYL-C (VCFLCASSGHVE) no longer comprise a PHD domain. However, SMART analysis of the predicted N-FRYL-MLL-C detected a PHD 1 domain (GKTLDFHFDISEFVYCQVCCEPFHKFCLEENERPLEDQLENWCCRRCK) with the first 12 amino acids contributed by FRYL (plain text) and the remaining C terminal amino acids (bold) derived from MLL. Therefore the predicted N-FRYL-MLL-C still contains 3 PHD domains.