Human Gene Set: ROSS_LEUKEMIA_WITH_MLL_FUSIONS


Standard name ROSS_LEUKEMIA_WITH_MLL_FUSIONS
Systematic name M12695
Brief description Top 100 probe sets associated with MLL fusions [GeneID=4297] irrespective of the lineage of the pediatric acute leukemia.
Full description or abstract Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15226186   Authors: Ross ME,Mahfouz R,Onciu M,Liu HC,Zhou X,Song G,Shurtleff SA,Pounds S,Cheng C,Ma J,Ribeiro RC,Rubnitz JE,Girtman K,Williams WK,Raimondi SC,Liang DC,Shih LY,Pui CH,Downing JR
Exact source Table 13S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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