Human Gene Set: DUNNE_TARGETS_OF_AML1_MTG8_FUSION_DN


Standard name DUNNE_TARGETS_OF_AML1_MTG8_FUSION_DN
Systematic name M6469
Brief description Genes down-regulated in Kasumi-1 cells (acute myeloid leukaemia (AML) with the t(8;21) translocation) after knockdown of the AML1 MTG8 fusion [GeneID=861;862] by RNAi.
Full description or abstract The chromosomal translocation t(8;21) is associated with 10-15% of all cases of acute myeloid leukaemia (AML). The resultant fusion protein AML1/MTG8 interferes with haematopoietic gene expression and is an important regulator of leukaemogenesis. We studied the effects of small interfering RNA (siRNA)-mediated AML1/MTG8 depletion on global gene expression in t(8;21)-positive leukaemic cell lines and in primary AML blasts using cDNA arrays, oligonucleotide arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR). Suppression of AML1/MTG8 results in the increased expression of genes associated with myeloid differentiation, such as AZU1, BPI, CTSG, LYZ and RNASE2 as well as of antiproliferative genes such as IGFBP7, MS4A3 and SLA both in blasts and in cell lines. Furthermore, expression levels of several genes affiliated with drug resistance or indicative of poor prognosis AML (BAALC, CD34, PRG2, TSPAN7) are affected by AML1/MTG8 depletion. In conclusion, siRNA-mediated suppression of AML1/MTG8 cause very similar changes in gene expression pattern in t(8;21)-positive cell lines and in primary AML blasts. Furthermore, the results suggest that the specific targeting of AML1/MTG8 function may be a promising approach for complementing existing treatment strategies.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16652140   Authors: Dunne J,Cullmann C,Ritter M,Soria NM,Drescher B,Debernardi S,Skoulakis S,Hartmann O,Krause M,Krauter J,Neubauer A,Young BD,Heidenreich O
Exact source Table 1-2: siAGF1/siAGF6 < 1
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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Version history 3.0: First introduced


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