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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

MLL is fused to EB1 (MAPRE1), which encodes a microtubule-associated protein, in a patient with acute lymphoblastic leukemia.

We have shown that the EB1 (MAPRE1) gene, at 20q11.2, is fused to MLL in an adult patient with pro-B acute lymphoblastic leukemia. Southern blot analysis indicated that a rearrangement of the MLL gene was involved in the chromosomal abnormality. cDNA panhandle polymerase chain reaction (PCR) identified the fusion transcript, in which MLL exon 6 was fused in-frame with EB1 exon 5. The presence of the MLL-EB1 and the reciprocal EB1- MLL fusion transcripts was verified by reverse-transcription PCR. EB1 is the first gene on chromosome 20 found to fuse with MLL. The genomic break junctions of MLL-EB1 and EB1- MLL were amplified by long-distance PCR. Sequencing of the break junctions revealed that multiple DNA breaks had occurred and that the DNA fragments flanked by these breaks had been duplicated, deleted, or inverted. Nontemplate DNA segments of 2 bp also were detected at the breakpoints on derivative chromosomes 11 and 20. These features indicate that this translocation likely resulted from the DNA damage-repair pathway. EB1 is a microtubule- associated protein that interacts with the colorectal adenomatous polyposis coli tumor-suppressor protein and plays important roles in regulating microtubule dynamics, cell polarity, and chromosome stability. Immunofluorescence staining demonstrated that the MLL-EB1 fusion proteins were localized in the nuclei.[1]


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