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MLL rearrangements in pediatric ALL and AML: MLL specific and lineage specific signatures

ABSTRACT: Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements. Gene expression signatures of acute lymphoblastic and myeloblastic leukemia samples with and without MLL rearrangements were analyzed using paired supervised analyses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE14062 | GEO | 2009/07/22

SECONDARY ACCESSION(S): PRJNA112429

REPOSITORIES: GEO

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Transcription profiling of human lymphoblastic and myeloblastic leukemia samples with and without MLL rearrangements specific and lineage specific signatures

Project description:Gene expression analysis identified a MLL translocation-specific signature of differentially expressed genes discriminating ALL and AML with and without MLL rearrangements. Gene expression signatures of acute lymphoblastic and myeloblastic leukemia samples with and without MLL rearrangements were analyzed using paired supervised analyses. Experiment Overall Design: ALL and AML patients with and without MLL rearrangements have been studied using paired class comparison (SAM) and class prediction (PAM) analyses.

2009-08-07 | E-GEOD-14062 | biostudies-arrayexpress

Histone 3 lysine 9 methylation balance controls transient site-specific DNA amplification and genomic rearrangements of Mixed Lineage Leukemia (MLL)

Project description:DNA amplifications and rearrangements are observed in cancer. In infant and adult leukemia as well as therapy-induced leukemia, MLL/KMT2A amplifications and translocations are prevalent. To date, the exact molecular contributor(s) to these alterations are unclear. In this study, we demonstrate that histone H3 K9 mono- and di-methylation (H3K9me1/2) balance at the MLL/KMT2A locus is regulating the amplifications and rearrangements. This balance is controlled by the cross-talk between lysine demethylase KDM3B and methyltransferase G9a/EHMT2. KDM3B loss or chemical suppression increases H3K9me1/2 and reduced CTCF occupancy in KMT2A, and in turn, promotes amplification and rearrangements. Reducing CTCF levels was also sufficient to generate these alterations. Furthermore, Doxorubicin (Dox), which promotes MLL/KMT2A amplifications and rearrangements, suppresses KDM3B and CTCF protein levels. By suppressing G9a or overexpressing KDM3B, the Dox induced MLL/KMT2A alterations are rescued. Therefore, MLL/KMT2A induced amplifications and rearrangements are controlled by distinct epigenetic enzymes that are druggable, which has clinical implications.

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A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia [RNA-seq]

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