Oncotarget

Research Perspectives:

FLT3 in lineage specification and plasticity

Sarah Greenblatt and Donald Small _

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Oncotarget. 2012; 3:576-580. https://doi.org/10.18632/oncotarget.499

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Abstract

Sarah Greenblatt1 and Donald Small1,2

1 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD

2 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD

Correspondence:

Donald Small, email:

Keywords: FLT3, B220, leukemia, lineage, differentiation

Received: May 14, 2012, Accepted: May 26, 2012, Published: May 27, 2012

Abstract

FLT3 is a receptor tyrosine kinase that is expressed in CD34+ hematopoietic stem/progenitor cells (HSPCs) and is important for both normal myeloid and lymphoid differentiation. FLT3 expression in Pax5 negative lymphoid precursors coincides with a window of multilineage differentiation potential in mice and humans. Recent work has shown that FLT3 activating mutations can collaborate with a Nup98-HoxD13 mutation to induce an aggressive acute leukemia. The leukemic initiating population in this model displayed properties of both lymphoid and myeloid precursors, making it a useful tool to study the role of FLT3 in lineage plasticity. Through a variety of assays, the leukemic initiating population was shown to be restricted to myeloid differentiation, suggesting that the B-lineage properties in these cells are due to the priming of lymphoid transcription programs in multipotent progenitors rather than a true capacity for B-cell maturation. The development of an undifferentiated myeloid leukemia in this model, also has implications for the role of FLT3 in the inhibition of myeloid differentiation. Here we discuss the insights gained from this model.


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