ArrayExpress Uploaderarrayexpress_sid728706Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of...E-GEOD-46797/profile/8773/arrayexpressuploader06acute lymphoblastic leukemiacancercellleukemialymphoblastic leukemiaproteinspleenstem cellDec.12, 2014Falseexpression-data-from-c-myc-notch1-t-all-initiatingE-GEOD-46797_A-AFFY-45Expression data from c-Myc+ Notch1 T-ALL initiating cellsNov.12, 2014Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Three independent Notch1 T-ALL were derived on c-Myc-GFP background and sorted from the spleen of leukemic mice on the basis of GFP expression for RNA extraction and hybridization on Affymetrix microarrayshttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-46797mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-46797/samples/