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Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.

Sykes DB1, Kfoury YS2, Mercier FE2, Wawer MJ3, Law JM4, Haynes MK5, Lewis TA6, Schajnovitz A2, Jain E7, Lee D2, Meyer H8, Pierce KA9, Tolliday NJ3, Waller A5, Ferrara SJ3, Eheim AL8, Stoeckigt D8, Maxcy KL7, Cobert JM7, Bachand J7, Szekely BA7, Mukherjee S10, Sklar LA5, Kotz JD6, Clish CB9, Sadreyev RI11, Clemons PA6, Janzer A8, Schreiber SL12, Scadden DT13.
Cell.Cell.2016 Sep 22;167(1):171-186.e15. doi: 10.1016/j.cell.2016.08.057. Epub 2016 Sep 15.
While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the obse
PMID 27641501

Dysplastic erythroid precursors in the myelodysplastic syndromes and the acute myeloid leukemias: Is there biologic significance? (How should blasts be counted?).

Bennett JM1, Tuechler H2, Aul C3, Strupp C4, Germing U4.
Leukemia research.Leuk Res.2016 Aug;47:63-9. doi: 10.1016/j.leukres.2016.05.006. Epub 2016 May 12.
The role of bone marrow dysplastic erythroid precursors (EP) in both MDS and AML has been the subject of considerable debate over the past several decades. We have analyzed a large series of adults with MDS and focused on whether any% of EP identified in the bone marrow aspirates of over 1400 patien
PMID 27258735

Liu W1, Wu M2, Huang Z2, Lian J2, Chen J2, Wang T3, Leung AY4, Liao Y1,5, Zhang Z1,6, Liu Q7, Yen K2, Lin S8, Zon LI9, Wen Z3, Zhang Y2, Zhang W1,2.
Leukemia.Leukemia.2016 Jul 26. doi: 10.1038/leu.2016.170. [Epub ahead of print]
The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we repor
PMID 27457538