Secondary acute myeloid leukemia arising early after cyclophosphamide treatment.

Background: Acute myeloid leukemia (AML) can develop secondary to drug treatment. This phenomenon has been placed under the title "Therapy Related Acute Myeloid Leukemias and Myelodysplastic Syndromes" in the WHO classification of AML. Cyclophosphamide, which is used in various malignancies and rheumatological diseases, is an alkylating agent that plays a significant role in therapy related AML.

PDK1 attenuation fails to prevent tumor formation in PTEN-deficient transgenic mouse models.

PDK1 activates AKT suggesting that PDK1 inhibition might suppress tumor development. However, while PDK1 has been investigated intensively as an oncology target, selective inhibitors suitable for in vivo studies have remained elusive. In this study we present the results of in vivo PDK1 inhibition through a universally applicable RNAi approach for functional drug target validation in oncogenic pathway contexts.