This project contains all information pertaining to the replication of key experiments from this paper. It includes the detailed protocols, including reagents and author clarifications. We also include any comments from other contributors, researchers from the Science Exchange network, and further information with the original authors that we have learned since the beginning of the project. When experimental studies begin all data collected will also be deposited here, including data analysis and eventually the final written report. <br> **Original citation:** Ward P.S., Patel J., Wise D.R., Abdel-Wahab O., Bennett B.D., Coller H.A., Cross J.R., Fantin V.R., Hedvat C.V., Perl A.E., Rabinowitz J.D., Carroll M., Su S.M., Sharp K.A., Levine R.L., Thompson C.B. The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting alpha-Ketoglutarate to 2-Hydroxyglutarate. Cancer Cell. 2010 Mar 16;17(3):225-34. doi: 10.1016/j.ccr.2010.01.020. <br> **Original paper abstract:** The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases with elevated 2HG possessed IDH1 mutations. The remaining cases with elevated 2HG had mutations in IDH2, the mitochondrial homolog of IDH1. These data demonstrate that a shared feature of all cancer-associated IDH mutations is production of the oncometabolite 2HG. Furthermore, AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.