Systematic name M7715
Brief description Top 100 genes negatively associated with T-cell acute lymphoblastic leukemia MLL T-ALL) expressing MLL-ENL fusion [GeneID=4297;4298].
Full description or abstract Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias. Gene expression analysis of MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has identified these cases as a unique subtype of leukemia, characterized by the expression of genes associated with both lymphoid and myeloid hematopoietic lineages. Here we show that MLL fusions also generate a distinct genetic subtype of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an early arrest in thymocyte differentiation, with suggestive evidence of commitment to the gammadelta lineage. Interestingly, multiple genes linked to cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P <.000 001, Fisher exact test). Overall, MLL T-ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes--HOXA9, HOXA10, and HOXC6--and the MEIS1 HOX coregulator (P <.008, one-sided Wilcoxon test), a pattern of gene expression that was reiterated in MLL B-ALLs. However, expression of myeloid lineage genes, previously reported in MLL B-ALLs, was not identified in T-lineage cases with this abnormality, suggesting that myeloid gene dysregulation is dispensable in leukemic transformation mediated by MLL fusion proteins. Our findings implicate dysregulation of HOX gene family members as a dominant mechanism of leukemic transformation induced by chimeric MLL oncogenes.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12637319   Authors: Ferrando AA,Armstrong SA,Neuberg DS,Sallan SE,Silverman LB,Korsmeyer SJ,Look AT
Exact source Table 3S: negatively associated
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(show 15 gene sets from the same authors)
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Source species Homo sapiens
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Version history 3.0: Renamed from FERRANDO_MLL_T_ALL_DN

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