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Article Abstract
Activating colony-stimulating factor-3 receptor gene () mutations are recurrent in acute myeloid leukemia (AML) with t(8;21) translocation. However, the nature of oncogenic collaboration between alterations of and the t(8;21) associated fusion remains unclear. In CD34+ hematopoietic stem and progenitor cells from healthy donors, double oncogene expression led to a clonal advantage, increased self-renewal potential, and blast-like morphology and distinct immunophenotype. Gene expression profiling revealed hedgehog signaling as a potential mechanism, with upregulation of constituting a putative pharmacological target. Both primary hematopoietic cells and the t(8;21) positive AML cell line SKNO-1 showed increased sensitivity to the GLI inhibitor GANT61 when expressing T618I. Our findings suggest that during leukemogenesis, the fusion and mutation act in a synergistic manner to alter hedgehog signaling, which can be exploited therapeutically.
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| http://dx.doi.org/10.1097/HS9.0000000000000958 | DOI Listing |
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