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19549311
MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures.

BMC Med Genomics, 2009/6/23;2:36.

Zangrando A[1], Dell'orto MC, Te Kronnie G, Basso G

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PMID: 19549311DOI: 10.1186/1755-8794-2-36

Impact factor: 3.622

Abstract
background: The 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.
methods: Using Affymetrix(R) 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.
results: We 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.
conclusion: Our 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.
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