Conference Proceedings
The Transcription Factor PU.1 Controls a Reversible Differentiation Program in Acute Myeloid Leukemia
Mark D McKenzie, Margherita Ghisi, Luisa Cimmino, Michael Erlichster, Ethan P Oxley, Cynthia Liu, Matthew T Witkowski, Grace Liu, Aleksandar Dakic, Emilia Simankowicz, Ladina DiRago, Donald Metcalf, Stephen L Nutt, Meaghan Wall, Matthew E Ritchie, Johannes Zuber, Ross A Dickins
BLOOD | AMER SOC HEMATOLOGY | Published : 2016
Abstract
Abstract Background: Acute myeloid leukemia (AML) is an aggressive malignancy characterized by clonal expansion of transformed myeloid precursors that fail to differentiate into mature cells. Since myeloid lineage maturation curbs self-renewal and is considered irreversible, engaging this process in AML is an attractive therapeutic strategy. Results: Normal myeloid differentiation requires the transcription factor PU.1 (SPI1), which is functionally compromised in several AML subtypes and is directly inhibited by the recurrent fusion oncoproteins AML1-ETO and PML-RARA. To examine the importance of PU.1 suppression in AML maintenance in vivo, we have combined RNAi..
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