Molecular basis of polycythemic disorders due to aberrant hypoxia sensing and its relevance to acute leukemia

The author of this lecture has been especially honored to be selected to deliver the Ernest Beutler Memorial Lecture at the Acute Leukemia Forum 2012 and to write this overview. Ernest Beutler was the pivotal influence in my introduction to academic life, and his contribution to hematology in the last 5 decades was unsurpassed. Taking a cue from Ernie's example, I have elected in the keynote speech and this brief treatise, to start with an unconventional introduction and to expand on some discoveries made in my laboratory. Then I will extend these findings to the focus of the Acute Leukemia Forum to address potentially new approaches to therapies of acute leukemias. Somatic and germline mutations of acute leukemias are unfortunately caused by arrays of somatic and germline mutations. Simultaneous targeting of so many mutations makes it not possible to efficiently target all for cure. Albeit we should be aware that we should not in the near future ignore targeted therapy of those functionally important genetic and epigenetic events that are either initiating or contributing to aggressivity of acute leukemia, as these may be ameliorated by targeted intervention against one, or even a few together, of these defined molecular lesions. Yet, leukemic cells, like other cancer cells, have the unique metabolic feature to generate energy, referred as the Warburg effect, which can potentially be targeted to suppress or even eradicate cancer.