Abstract
BackgroundThe presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL) and myeloblastic leukemia (AML), with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes.MethodsUsing Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set) + 78 (test set) ALL and AML patients with (24+13) and without (116+65) MLL rearrangements have been investigated performing class comparison (SAM) and class prediction (PAM) analyses.ResultsWe identified a MLL translocation-specific (379 probes) signature and a phenotype-specific (622 probes) signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements.ConclusionOur study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.
Highlights
The presence of Mixed Lineage Leukemia (MLL) rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained
The present study encompasses the efforts to clarify the relations between MLL translocation and acute leukemias in pediatric patients: we identified common MLL-related markers that are shared between leukemias with different phenotypes and investigated the role of MLL aberration in acute leukemias with different lineage origin
We assessed the key role of previously unexplored genes to characterize MLL translocation as well as the impact of wellknown genes in separating acute leukemia samples according to phenotype origin
Summary
The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. The present study encompasses the efforts to clarify the relations between MLL translocation and acute leukemias in pediatric patients: we identified common MLL-related markers that are shared between leukemias with different phenotypes (translocation-related signature) and investigated the role of MLL aberration in acute leukemias with different lineage origin (phenotype-related signature). To this end, two independent cohorts of 140 (training set) and 78 (test set) pediatric patients with ALL/MLL+, AML/MLL+, ALL/MLLand AML/MLL- have been inspected using gene expression profiling. We assessed the key role of previously unexplored genes to characterize MLL translocation as well as the impact of wellknown genes in separating acute leukemia samples according to phenotype origin
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