Genomics

Dataset Information

153

Instructive role of MLL fusion proteins revealed by a faithful model of t(4;11) proB acute lymphoblastic leukemia


ABSTRACT: The t(4;11)(q21;q23) fuses MLL to AF4, the most common MLL fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells to generate a faithful model of t(4;11) proB ALL that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a distinct B-ALL from MLL-AF9 through differential DNA binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. We observed this incongruity in t(4;11) patients who evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis. Overall design: MLL-AF4 ChIP-seq expreiment has been used in this study

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: Salam Adli Assi  

PROVIDER: GSE84116 | GEO | 2016-11-23

SECONDARY ACCESSION(S): PRJNA328075

REPOSITORIES: GEO

altmetric image

Publications


The t(4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells, thereby generating a model of t(4;11) pro-B acute lymphoblastic leukemia (ALL) that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B ALL distinct from MLL-AF9 through differential genomic  ...[more]

Similar Datasets

| GSE76978 | GEO
| GSE85988 | GEO
2015-12-17 | E-GEOD-74812 | ArrayExpress
2012-05-31 | E-GEOD-38339 | ArrayExpress
| GSE12362 | GEO
| GSE103947 | GEO
| GSE12361 | GEO
2008-11-13 | E-GEOD-12313 | ArrayExpress
2008-11-04 | GSE12313 | GEO
2018-05-25 | PXD009338 | Pride