Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia

Oncotarget

Volumn 5, Issue 23, 2014, Pages 12371-12382

  Alachkar, Houda ^a   Mutonga, Martin B G ^a   Metzeler, Klaus H ^b,c   Fulton, Noreen ^a   Malnassy, Gregory ^a   Herold, Tobias ^b,c   Spiekermann, Karsten ^b,c   Bohlander, Stefan K ^d   Hiddemann, Wolfgang ^b,c   Matsuo, Yo ^e   Stock, Wendy ^a   Nakamura, Yusuke ^a  

^a UNIVERSITY OF CHICAGO   (United States)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^c INSTITUTE OF EPIDEMIOLOGY   (Germany)

^d UNIVERSITY OF AUCKLAND   (New Zealand)

^e Research and Development Division   (Japan)

Author keywords

AML; MELK; OTS167

Indexed keywords

ANTILEUKEMIC AGENT; MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE PROTEIN; OTS 167; PROTEIN FOXM1; PROTEIN KINASE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; ENZYME INHIBITOR; MELK PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

ACUTE GRANULOCYTIC LEUKEMIA; ADULT; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL DESTRUCTION; CANCER INHIBITION; CELL DIFFERENTIATION; CELL MIGRATION; CELL VIABILITY; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RESEARCH; DRUG SCREENING; ENZYME INHIBITION; GENE EXPRESSION; HUMAN; HUMAN CELL; LEUKEMIA CELL; MAJOR CLINICAL STUDY; MOUSE; NONHUMAN; PROTEIN EXPRESSION; ACUTE MYELOID LEUKEMIA; ADOLESCENT; APOPTOSIS; CELL CYCLE; DNA MICROARRAY; DRUG EFFECTS; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; GENETIC TRANSFECTION; KAPLAN MEIER METHOD; MALE; METABOLISM; MIDDLE AGED; MORTALITY; REAL TIME POLYMERASE CHAIN REACTION; TUMOR CELL LINE; WESTERN BLOTTING; YOUNG ADULT;

ADOLESCENT; ADULT; APOPTOSIS; BLOTTING, WESTERN; CELL CYCLE; CELL LINE, TUMOR; ENZYME INHIBITORS; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; KAPLAN-MEIER ESTIMATE; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PROTEIN-SERINE-THREONINE KINASES; REAL-TIME POLYMERASE CHAIN REACTION; TRANSFECTION; YOUNG ADULT;

EID: 84920017381     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2642     Document Type: Article

References (30)

1. Heyer BS, Warsowe J, Solter D, Knowles BB, Ackerman SL. New member of the snf1/ampk kinase family, melk, is expressed in the mouse egg and preimplantation embryo. Mol Reprod Dev. 1997;47:148-156.
2. Badouel C, Chartrain I, Blot J, Tassan JP. Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit. Exp Cell Res. 2010;316:2166-2173.
3. Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T. Involvement of maternal embryonic leucine zipper kinase (melk) in mammary carcinogenesis through interaction with bcl-g, a pro-apoptotic member of the bcl-2 family. Breast Cancer Res. 2007;9:R17.
4. Gil M, Yang Y, Lee Y, Choi I, Ha H. Cloning and expression of a cdna encoding a novel protein serine/ threonine kinase predominantly expressed in hematopoietic cells. Gene. 1997;195:295-301.
5. Easterday MC, Dougherty JD, Jackson RL, Ou J, Nakano I, Paucar AA, Roobini B, Dianati M, Irvin DK, Weissman IL, Terskikh AV, Geschwind DH, Kornblum HI. Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations. Dev Biol. 2003;264:309-322.
6. Nakano I, Masterman-Smith M, Saigusa K, Paucar AA, Horvath S, Shoemaker L, Watanabe M, Negro A, Bajpai R, Howes A, Lelievre V, Waschek JA, Lazareff JA, et al. Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells. J Neurosci Res. 2008;86:48-60.
7. Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP. Maternal embryonic leucine zipper kinase/ murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers. Cancer Res. 2005;65:9751-9761.
8. Marie SK, Okamoto OK, Uno M, Hasegawa AP, Oba-Shinjo SM, Cohen T, Camargo AA, Kosoy A, Carlotti CG Jr, Toledo S, Moreira-Filho CA, Zago MA, Simpson AJ, Caballero OL. Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas. Int J Cancer. 2008;122:807-815.
9. Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS. Analysis of gene expression and chemoresistance of cd133+ cancer stem cells in glioblastoma. Mol Cancer. 2006;5:67.
10. Kuner R, Falth M, Pressinotti NC, Brase JC, Puig SB, Metzger J, Gade S, Schäfer G, Bartsch G, Steiner E, Klocker H, Sültmann H. The maternal embryonic leucine zipper kinase (melk) is upregulated in high-grade prostate cancer. J Mol Med (Berl). 2013;91:237-248.
11. Pickard MR, Green AR, Ellis IO, Caldas C, Hedge VL, Mourtada-Maarabouni M, et al. Dysregulated expression of fau and melk is associated with poor prognosis in breast cancer. Breast Cancer Res. 2009;11:R60.
12. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Mourtada-Maarabouni M, Williams GT. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci U S A. 2004;101:9309-9314.
13. Davezac N, Baldin V, Blot J, Ducommun B, Tassan JP. Human peg3 kinase associates with and phosphorylates cdc25b phosphatase: A potential role for peg3 in cell cycle regulation. Oncogene. 2002;21:7630-7641.
14. Beullens M, Vancauwenbergh S, Morrice N, Derua R, Ceulemans H, Waelkens E, Bollen M. Substrate specificity and activity regulation of protein kinase melk. J Biol Chem. 2005;280:40003-40011.
15. Joshi K, Banasavadi-Siddegowda Y, Mo X, Kim SH, Mao P, Kig C, Nardini D, Sobol RW, Chow LM, Kornblum HI, Waclaw R, Beullens M, Nakano I. Melk dependent foxm1 phosphorylation is essential for proliferation of glioma stem cells. Stem cells. 2013;31:1051-1063.
16. Nakamura, S., Hirano I, Okinaka K, Takemura T, Yokota D, Ono T, Shigeno K, Shibata K, Fujisawa S, Ohnishi K. The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia. Carcinogenesis, 2010;31(11):2012-21.
17. Saito R, Tabata Y, Muto A, Arai K, Watanabe S. Melk-like kinase plays a role in hematopoiesis in the zebra fish. Mol Cell Biol. 2005;25:6682-6693.
18. Chung S, Suzuki H, Miyamoto T, Takamatsu N, Tatsuguchi A, Ueda K, Kijima K, Nakamura Y, Matsuo Y. Development of an orally-administrative melk-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget. 2012;3:1629-1640.
19. Chung S, Nakamura Y. Melk inhibitor, novel molecular targeted therapeutics for human cancer stem cells. Cell cycle. 2013;12:1655-1656.
20. Li Z, Herold T, He C, Valk PJ, Chen P, Jurinovic V, Mansmann U, Radmacher MD, Maharry KS, Sun M, Yang X, Huang H, Jiang X. et al. Identification of a 24-gene prognostic signature that improves the european leukemianet risk classification of acute myeloid leukemia: An international collaborative study. J Clin Oncol. 2013;31:1172-1181.
21. Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J, Oshima RG, Terskikh AV. Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumorinitiating cells in vivo. Cancer Res. 2010;70:8863-8873.
22. Nakano, I., Transcription factors as master regulator for cancer stemness: remove milk from fox? Expert Rev Anticancer Ther, 2014. 14(8): 873-5.
23. Zhang, X., Zeng J, Zhou M, Li B, Zhang Y, Huang T, Wang L, Jia J, Chen C. The tumor suppressive role of miRNA-370 by targeting FoxM1 in acute myeloid leukemia. Mol Cancer, 2012. 11:56.
24. Liu LL, Zhang DH, Mao X, Zhang XH, Zhang B. Overexpression of FoxM1 is associated with adverse prognosis and FLT3-ITD in acute myeloid leukemia. Biochem Biophys Res Commun, 2014. 446(1):280-5.
25. Kig C, Beullens M, Beke L, Van Eynde A, Linders JT, Brehmer D, Bollen M. Maternal embryonic leucine zipper kinase (melk) reduces replication stress in glioblastoma cells. J Biol Chem. 2013;288:24200-24212.
26. Alachkar H, Santhanam R, Harb JG, Lucas DM, Oaks JJ, Hickey CJ, Pan L, Kinghorn AD, Caligiuri MA, Perrotti D, Byrd JC, Garzon R, Grever MR, et al. Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits flt3 and mir-155 expressions in acute myeloid leukemia. J Hematol Oncol. 2013;6:21.
27. Alachkar H, Santhanam R, Maharry K, Metzeler KH, Huang X, Kohlschmidt J, Mendler JH, Benito JM, Hickey C, Neviani P, Dorrance AM, Anghelina M, Khalife J, et al. Sparc promotes leukemic cell growth and predicts acute myeloid leukemia outcome. J Clin Invest. 2014;124:1512-1524.
28. Voermans C, van Heese WP, de Jong I, Gerritsen WR, van Der Schoot CE. Migratory behavior of leukemic cells from acute myeloid leukemia patients. Leukemia. 2002;16:650-657.
29. Ranganathan P, Yu X, Na C, Santhanam R, Shacham S, Kauffman M, Walker A, Klisovic R, Blum W, Caligiuri M, Croce CM, Marcucci G, Garzon R. et al. Preclinical activity of a novel crm1 inhibitor in acute myeloid leukemia. Blood. 2012;120:1765-1773.
30. Marcucci G, Maharry K, Wu YZ, Radmacher MD, Mrozek K, Margeson D, Holland KB, Whitman SP, Becker H, Schwind S, Metzeler KH, Powell BL, Carter TH et al. Idh1 and idh2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: A cancer and leukemia group b study. J Clin Oncol. 2010;28:2348-2355.