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Comment
. 2017 Jan;27(1):9-10.
doi: 10.1038/cr.2016.130. Epub 2016 Nov 11.

A new target for differentiation therapy in AML

Peilin Ma  1 , Weihua Song  1 , Jay L Hess  1
Affiliations
Comment

A new target for differentiation therapy in AML

Peilin Ma et al. Cell Res. 2017 Jan.

Abstract

Despite major advances in understanding the genetics and epigenetics of acute myelogenous leukemia, there is still a great need to develop more specific and effective therapies. High throughput approaches involving either genetic approaches or small molecule inhibitor screens are beginning to identify promising new therapeutic targets.

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Figures

Figure 1
Figure 1
Identification of DHODH as a target for differentiation therapy. Myeloid cells were conditionally immortalized by expression of estrogen receptor-HoxA9 (ER-HOXA9) fusion protein in bone marrow cells in which GFP is inserted into the lysozyme locus. Removal of β-estradiol (E2) causes ER-HOXA9 to remain in the cytoplasm resulting in myeloid differentiation and expression of GFP and granulocyte markers such as CD11b. Screening 330 000 compounds led to the identification of small molecules promoting myeloid differentiation. Ultimately the target of the inhibitors was identified as DHODH, a key regulator of pyrimidine biosynthesis.
See this image and copyright information in PMC

Comment on

  • Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.
    Sykes DB, Kfoury YS, Mercier FE, Wawer MJ, Law JM, Haynes MK, Lewis TA, Schajnovitz A, Jain E, Lee D, Meyer H, Pierce KA, Tolliday NJ, Waller A, Ferrara SJ, Eheim AL, Stoeckigt D, Maxcy KL, Cobert JM, Bachand J, Szekely BA, Mukherjee S, Sklar LA, Kotz JD, Clish CB, Sadreyev RI, Clemons PA, Janzer A, Schreiber SL, Scadden DT. Sykes DB, et al. Cell. 2016 Sep 22;167(1):171-186.e15. doi: 10.1016/j.cell.2016.08.057. Epub 2016 Sep 15. Cell. 2016. PMID: 27641501 Free PMC article.

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