SYK Is a Critical Regulator of FLT3 in Acute Myeloid Leukemia

Cancer Cell

Volumn 25, Issue 2, 2014, Pages 226-242

  Puissant, Alexandre ^a   Fenouille, Nina ^b   Alexe, Gabriela ^a,c,d   Pikman, Yana ^a   Bassil, Christopher F ^a   Mehta, Swapnil ^a   Du, Jinyan ^c   Kazi, Julhash U ^e   Luciano, Frédéric ^f   Rönnstrand, Lars ^e   Kung, Andrew L ^g   Aster, Jon C ^a   Galinsky, Ilene ^a   Stone, Richard M ^a   DeAngelo, Daniel J ^a   Hemann, Michael T ^b   Stegmaier, Kimberly ^a,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d BOSTON UNIVERSITY   (United States)

^e LUND UNIVERSITY   (Sweden)

^f INSERM   (France)

^g NewYork Presbyterian Hospital   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD135 ANTIGEN; DOXYCYCLINE; FLUOROURACIL; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE SYK;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME BINDING; ENZYME PHOSPHORYLATION; GENE EXPRESSION; HUMAN; HUMAN CELL; MALE; MALIGNANT TRANSFORMATION; MOUSE; MYELOPROLIFERATIVE DISORDER; NONHUMAN; ONCOGENE MYC; PRIORITY JOURNAL; PROTEIN TARGETING; THERAPY RESISTANCE; TRANSACTIVATION; TUMOR GROWTH;

ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BLOTTING, WESTERN; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; CELLS, CULTURED; DRUG RESISTANCE, NEOPLASM; FLUOROURACIL; FMS-LIKE TYROSINE KINASE 3; HUMANS; IMMUNOENZYME TECHNIQUES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LEUKEMIA, MYELOID, ACUTE; MICE; MICE, INBRED BALB C; MUTATION; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SURVIVAL RATE;

EID: 84893550362     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2014.01.022     Document Type: Article

References (32)

1. Bernt K.M., Zhu N., Sinha A.U., Vempati S., Faber J., Krivtsov A.V., Feng Z., Punt N., Daigle A., Bullinger L., et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 2011, 20:66-78.
2. Braselmann S., Taylor V., Zhao H., Wang S., Sylvain C., Baluom M., Qu K., Herlaar E., Lau A., Young C., et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J.Pharmacol. Exp. Ther. 2006, 319:998-1008.
3. Daigle S.R., Olhava E.J., Therkelsen C.A., Majer C.R., Sneeringer C.J., Song J., Johnston L.D., Scott M.P., Smith J.J., Xiao Y., et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011, 20:53-65.
4. DeAngelo D.J., Stone R.M., Heaney M.L., Nimer S.D., Paquette R.L., Klisovic R.B., Caligiuri M.A., Cooper M.R., Lecerf J.M., Karol M.D., et al. Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood 2006, 108:3674-3681.
5. Deshpande A.J., Bradner J., Armstrong S.A. Chromatin modifications as therapeutic targets in MLL-rearranged leukemia. Trends Immunol. 2012, 33:563-570.
6. Fischer T., Stone R.M., Deangelo D.J., Galinsky I., Estey E., Lanza C., Fox E., Ehninger G., Feldman E.J., Schiller G.J., et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J.Clin. Oncol. 2010, 28:4339-4345.
7. Friedberg J.W., Sharman J., Sweetenham J., Johnston P.B., Vose J.M., Lacasce A., Schaefer-Cutillo J., De Vos S., Sinha R., Leonard J.P., et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2010, 115:2578-2585.
8. Griffith J., Black J., Faerman C., Swenson L., Wynn M., Lu F., Lippke J., Saxena K. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol. Cell 2004, 13:169-178.
9. Hahn C.K., Berchuck J.E., Ross K.N., Kakoza R.M., Clauser K., Schinzel A.C., Ross L., Galinsky I., Davis T.N., Silver S.J., et al. Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell 2009, 16:281-294.
10. Katsumi A., Kiyoi H., Abe A., Tanizaki R., Iwasaki T., Kobayashi M., Matsushita T., Kaibuchi K., Senga T., Kojima T., et al. FLT3/ ITD regulates leukaemia cell adhesion through α4β1 integrin and Pyk2 signalling. Eur. J. Haematol. 2011, 86:191-198.
11. Keshvara L.M., Isaacson C., Harrison M.L., Geahlen R.L. Syk activation and dissociation from the B-cell antigen receptor is mediated by phosphorylation of tyrosine 130. J.Biol. Chem. 1997, 272:10377-10381.
12. Knapper S., Burnett A.K., Littlewood T., Kell W.J., Agrawal S., Chopra R., Clark R., Levis M.J., Small D. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 2006, 108:3262-3270.
13. Kuno Y., Abe A., Emi N., Iida M., Yokozawa T., Towatari M., Tanimoto M., Saito H. Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). Blood 2001, 97:1050-1055.
14. Ley T., Miller C., Ding L., Raphael B., Mungall A., Robertson A., Hoadley K., Triche T.J., Laird P., Baty J., et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N.Engl. J. Med. 2013, 368:2059-2074. Cancer Genome Atlas Research Network.
15. Luo H., Li Q., O'Neal J., Kreisel F., Le Beau M.M., Tomasson M.H. c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood 2005, 106:2452-2461.
16. Miller P.G., Al-Shahrour F., Hartwell K.A., Chu L.P., Järås M., Puram R.V., Puissant A., Callahan K.P., Ashton J., McConkey M.E., et al. InVivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 2013, 24:45-58.
17. Mócsai A., Ruland J., Tybulewicz V.L. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat. Rev. Immunol. 2010, 10:387-402.
18. Moon K.D., Post C.B., Durden D.L., Zhou Q., De P., Harrison M.L., Geahlen R.L. Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase. J.Biol. Chem. 2005, 280:1543-1551.
19. Moy L.Y., Jia Y., Caniga M., Lieber G., Gil M., Fernandez X., Sirkowski E., Miller R., Alexander J.P., Lee H.H., et al. Inhibition of spleen tyrosine kinase attenuates allergen-mediated airway constriction. Am. J. Respir. Cell Mol. Biol. 2013, 49:1085-1092.
20. 2 integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. Blood 2013, 121:3889-3899.
21. Patel J.P., Gönen M., Figueroa M.E., Fernandez H., Sun Z., Racevskis J., Van Vlierberghe P., Dolgalev I., Thomas S., Aminova O., et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N.Engl. J. Med. 2012, 366:1079-1089.
22. Pechloff K., Holch J., Ferch U., Schweneker M., Brunner K., Kremer M., Sparwasser T., Quintanilla-Martinez L., Zimber-Strobl U., Streubel B., et al. The fusion kinase ITK-SYK mimics a Tcell receptor signal anddrives oncogenesis in conditional mouse models of peripheral Tcell lymphoma. J.Exp. Med. 2010, 207:1031-1044.
23. Pratz K.W., Cortes J., Roboz G.J., Rao N., Arowojolu O., Stine A., Shiotsu Y., Shudo A., Akinaga S., Small D., et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 2009, 113:3938-3946.
24. Sexauer A., Perl A., Yang X., Borowitz M., Gocke C., Rajkhowa T., Thiede C., Frattini M., Nybakken G.E., Pratz K., et al. Terminal myeloid differentiation invivo is induced by FLT3 inhibition in FLT3/ITD AML. Blood 2012, 120:4205-4214.
25. Smith C.C., Wang Q., Chin C.S., Salerno S., Damon L.E., Levis M.J., Perl A.E., Travers K.J., Wang S., Hunt J.P., et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012, 485:260-263.
26. Spurgeon S.E., Coffey G., Fletcher L.B., Burke R., Tyner J.W., Druker B.J., Betz A., DeGuzman F., Pak Y., Baker D., et al. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function invitro and invivo and augments the activity of fludarabine in chronic lymphocytic leukemia. J.Pharmacol. Exp. Ther. 2013, 344:378-387.
27. Swords R., Freeman C., Giles F. Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia. Leukemia 2012, 26:2176-2185.
28. Umehara H., Huang J.Y., Kono T., Tabassam F.H., Okazaki T., Gouda S., Nagano Y., Bloom E.T., Domae N. Co-stimulation of Tcells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl. Int. Immunol. 1998, 10:833-845.
29. Weisberg E., Sattler M., Ray A., Griffin J.D. Drug resistance in mutant FLT3-positive AML. Oncogene 2010, 29:5120-5134.
30. Williams R.T., Roussel M.F., Sherr C.J. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. USA 2006, 103:6688-6693.
31. Wu J., Meng F., Lu H., Kong L., Bornmann W., Peng Z., Talpaz M., Donato N.J. Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib-resistant chronic myelogenous leukemia cells. Blood 2008, 111:3821-3829.
32. Zuber J., Shi J., Wang E., Rappaport A.R., Herrmann H., Sison E.A., Magoon D., Qi J., Blatt K., Wunderlich M., et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011, 478:524-528.