A hat trick for differentiation therapy?

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Science  21 Oct 2016:
Vol. 354, Issue 6310, pp. 298-299
DOI: 10.1126/science.354.6310.298-f

Most forms of acute myeloid leukemia (AML) are associated with a poor prognosis. One exception is acute promyelocytic leukemia, which is largely curable by two drugs, one originating from traditional Chinese medicine. Both drugs act by forcing leukemic precursor cells to differentiate into mature cell types that no longer divide. Given that all forms of AML are characterized by preleukemic myeloid cells whose differentiation is arrested, Sykes et al. performed an unbiased screen for compounds that induce myeloid differentiation. Unexpectedly, the most active compounds in mouse and human models were inhibitors of dihydroorotate dehydrogenase, an enzyme involved in pyrimidine biosynthesis. These inhibitors slowed AML development in mice and thus may merit further study as a therapy for the human disease.

Cell 167, 171 (2016).

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