t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5 ' MONOPHOSPATE SYNTHETASE) gene

The partner gene of MLL was identified in a patient with treatment-related acute myeloid leukemia in which the karyotype suggested t(3;11)(q25;q23). P rior therapy included the DNA topoisomerase II inhibitors, teniposide and d oxorubicin. Southern blot analysis indicated that the MLL gene was involved in the translocation. cDNA panhandle polymerase chain reaction (PCR) was u sed, which does not require partner gene specific primers, to identify the chimeric transcript Reverse-transcription of first-strand cDNAs with oligon ucleotides containing known MLL sequence at the 5' ends and random hexamers at the 3' ends generated templates with an intra-strand loop for PCR. In-f rame fusions of either MLL exon 7 or exon 8 with the GMPS (GUANOSINE 5'-MON OPHOSPHATE SYNTHETASE) gene from chromosome band 3q24 were detected. The fu sion transcript was alternatively spliced. Guanosine monophosphate syntheta se is essential for de novo purine synthesis. GMPS is the first partner gen e of MLL on chromosome 3q and the first gene of this type in leukemia-assoc iated translocations. (Blood. 2000;96: 4360-4362) (C) 2000 by The American Society of Hematology.