Scientific Publications

SYK Is a Critical Regulator of FLT3 in Acute Myeloid Leukemia.

Publication TypeJournal Article
AuthorsPuissant, A., Fenouille N., Alexe G., Pikman Y., Bassil CF, Mehta S., Du J., Kazi JU, Luciano F., Rönnstrand L., Kung AL, Aster J. C., Galinsky I., Stone RM, DeAngelo DJ, Hemann MT, and Stegmaier K.
AbstractCooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. Highly activated SYK is predominantly found in FLT3-ITD positive AML and cooperates with FLT3-ITD to activate MYC transcriptional programs. FLT3-ITD AML cells are more vulnerable to SYK suppression than FLT3 wild-type counterparts. In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy.
Year of Publication2014
JournalCancer cell
Volume25
Issue2
Pages226-42
Date Published (YYYY/MM/DD)2014/02/10
ISSN Number1535-6108
DOI10.1016/j.ccr.2014.01.022
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24525236?dopt=Abstract