Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia

Blood

Volumn 118, Issue 19, 2011, Pages 5235-5245

  Mizukawa, Benjamin ^a   Wei, Junping ^a,c   Shrestha, Mahesh ^a   Wunderlich, Mark ^a   Chou, Fu Sheng ^a   Griesinger, Andrea ^a   Harris, Chad E ^b   Kumar, Ashish R ^a   Zheng, Yi ^a   Williams, David A ^b   Mulloy, James C ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b HARVARD STEM CELL INSTITUTE   (United States)

^c R and D Systems Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; HYBRID PROTEIN; LENTIVIRUS VECTOR; MIXED LINEAGE LEUKEMIA PROTEIN AF9 FUSION PROTEIN; PROTEIN BCL 2; PROTEIN BCL XL; RAC1 PROTEIN; RAC2 PROTEIN; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER INHIBITION; CANCER SURVIVAL; CLONE; CONTROLLED STUDY; DRUG DOSE TITRATION; DRUG POTENTIATION; DRUG SCREENING; ENZYME INHIBITION; GENE SILENCING; HUMAN; HUMAN CELL; IC 50; LEUKEMOGENESIS; LOW DRUG DOSE; MOLECULARLY TARGETED THERAPY; MOUSE; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENIC MOUSE; WILD TYPE;

EID: 81155149508     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2011-04-351817     Document Type: Article

References (49)

1. Harrison CJ, Hills RK, Moorman AV, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. 2010;28(16):2674-2681.
2. Mueller D, Bach C, Zeisig D, et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood. 2007;110(13):4445-4454. (Pubitemid 351377811)
3. Bitoun E, Oliver PL, Davies KE. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum Mol Genet. 2007;16(1):92-106. (Pubitemid 46152547)
4. Mueller D, Garcia-Cuellar MP, Bach C, Buhl S, Maethner E, Slany RK. Misguided transcriptional elongation causes mixed lineage leukemia. PLoS Biol. 2009;7(11):e1000249.
5. Lin C, Smith ER, Takahashi H, et al. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol Cell. 2010;37(3):429-437.
6. Yokoyama A, Lin M, Naresh A, Kitabayashi I, Cleary ML. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell. 2010;17(2):198-212.
7. Mohan M, Herz HM, Takahashi YH, et al. Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev. 2010;24(6):574-589.
8. Barabe F, Kennedy JA, Hope KJ, Dick JE. Modeling the initiation and progression of human acute leukemia in mice. Science. 2007;316(5824):600-604. (Pubitemid 46683146)
9. Wei J, Wunderlich M, Fox C, et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell. 2008;13(6):483-495. (Pubitemid 351763903)
10. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818-822. (Pubitemid 44258912)
11. Somervaille TC, Cleary ML. Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell. 2006;10(4):257-268. (Pubitemid 44512188)
12. Corral J, Lavenir I, Impey H, et al. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell. 1996;85(6):853-861. (Pubitemid 26192136)
13. Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010;115(5):936-947.
14. Burridge K, Wennerberg K. Rho and Rac take center stage. Cell. 2004;116(2):167-179. (Pubitemid 38167310)
15. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247-269. (Pubitemid 41740635)
16. Haataja L, Groffen J, Heisterkamp N. Characterization of RAC3, a novel member of the Rho family. J Biol Chem. 1997;272(33):20384-20388. (Pubitemid 27355588)
17. Gu Y, Filippi MD, Cancelas JA, et al. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science. 2003;302(5644):445-449. (Pubitemid 37296270)
18. Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nat Med. 2005;11(8):886-891. (Pubitemid 41161122)
19. Yang FC, Atkinson SJ, Gu Y, et al. Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization. Proc Natl Acad Sci U S A. 2001;98(10):5614-5618. (Pubitemid 32435690)
20. Thomas EK, Cancelas JA, Chae HD, et al. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell. 2007;12(5):467-478. (Pubitemid 350046406)
21. Skorski T, Wlodarski P, Daheron L, et al. BCR/ABL-mediated leukemogenesis requires the activity of the small GTP-binding protein Rac. Proc Natl Acad Sci U S A. 1998;95(20):11858-11862. (Pubitemid 28460504)
22. Sengupta A, Arnett J, Dunn S, Williams DA, Cancelas JA. Rac2 GTPase deficiency depletes BCR-ABL- leukemic stem cells and progenitors in vivo. Blood. 2010;116(1):81-84.
23. Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-3687. (Pubitemid 39564445)
24. Muller LU, Schore RJ, Zheng Y, et al. Rac guanosine triphosphatases represent a potential target in AML. Leukemia. 2008;22(9):1803-1806.
25. Rozenveld-Geugien M, Baas IO, van Gosliga D, Vellenga E, Schuringa JJ. Expansion of normal and leukemic human hematopoietic stem/progenitor cells requires rac-mediated interaction with stromal cells. Exp Hematol. 2007;35(5):782-792. (Pubitemid 46601754)
26. Yang FC, Kapur R, King AJ, et al. Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells. Immunity. 2000;12(5):557-568.
27. Mulloy JC, Cammenga J, Berguido FJ, et al. Maintaining the self-renewal and differentiation potential of human CD34- hematopoietic cells using a single genetic element. Blood. 2003;102(13):4369-4376. (Pubitemid 37494097)
28. Wunderlich M, Chou FS, Link KA, et al. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia. 2010;24(10):1785-1788.
29. Feuring-Buske M, Gerhard B, Cashman J, Humphries RK, Eaves CJ, Hogge DE. Improved engraftment of human acute myeloid leukemia progenitor cells in beta 2-microglobulin-deficient NOD/SCID mice and in NOD/SCID mice transgenic for human growth factors. Leukemia. 2003;17(4):760-763. (Pubitemid 36519373)
30. Weber K, Bartsch U, Stocking C, Fehse B. A multicolor panel of novel lentiviral "gene ontology"(LeGO) vectors for functional gene analysis. Mol Ther. 2008;16(4):698-706. (Pubitemid 351426171)
31. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677-681. (Pubitemid 40825512)
32. Konopleva M, Contractor R, Tsao T, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006;10(5):375-388. (Pubitemid 44693472)
33. Jayanthan A, Incoronato A, Singh A, et al. Cytotoxicity, drug combinability, and biological correlates of ABT-737 against acute lymphoblastic leukemia cells with MLL rearrangement. Pediatr Blood Cancer. 2011;56(3):353-360.
34. Heyworth PG, Bohl BP, Bokoch GM, Curnutte JT. Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. J Biol Chem. 1994;269(49):30749-30752.
35. Velaithan R, Kang J, Hirpara JL, et al. The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity. Blood. 2011;117(23):6214-6226.
36. Oda H, Suzuki H, Sakai K, et al. Rac1-mediated Bcl-2 induction is critical in antigen-induced CD4 single-positive differentiation of a CD4-CD8-immature thymocyte line. J Leukoc Biol. 2007;81(2):500-508. (Pubitemid 46198402)
37. Gu Y, Siefring JE, Wang L, Chae HD, Bailey JR, Zheng Y. Oncogenic Vav1 induces Racdependent apoptosis via inhibition of Bcl-2 family proteins and collaborates with p53 deficiency to promote hematopoietic progenitor cell proliferation. Oncogene. 2006;25(28):3963-3972. (Pubitemid 43990752)
38. Wiederschain D, Kawai H, Shilatifard A, Yuan ZM. Multiple mixed lineage leukemia (MLL) fusion proteins suppress p53-mediated response to DNA damage. J Biol Chem. 2005;280(26):24315-24321. (Pubitemid 40934513)
39. Robinson BW, Behling KC, Gupta M, et al. Abundant anti-apoptotic BCL-2 is a molecular target in leukaemias with t(4;11) translocation. Br J Haematol. 2008;141(6):827-839. (Pubitemid 351724853)
40. Gandhi L, Camidge DR, Ribeiro de Oliveira M, et al. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011;29(7):909-916.
41. Mason KD, Carpinelli MR, Fletcher JI, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128(6):1173-1186. (Pubitemid 46427871)
42. Armstrong SA, Kung AL, Mabon ME, et al. Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 2003;3(2):173-183. (Pubitemid 37443389)
43. Carnicer MJ, Nomdedeu JF, Lasa A, et al. FLT3 mutations are associated with other molecular lesions in AML. Leuk Res. 2004;28(1):19-23. (Pubitemid 37433789)
44. Stubbs MC, Kim YM, Krivtsov AV, et al. MLL-AF9 and FLT3 cooperation in acute myelogenous leukemia: development of a model for rapid therapeutic assessment. Leukemia. 2008;22(1):66-77.
45. Sallmyr A, Fan J, Datta K, et al. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML. Blood. 2008;111(6):3173-3182.
46. Kawashima T, Bao YC, Nomura Y, et al. Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. J Cell Biol. 2006;175(6):937-946. (Pubitemid 44969199)
47. Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Hematol Oncol Clin North Am. 2010;24(1):35-63.
48. Kaspers GJ, Creutzig U. Pediatric acute myeloid leukemia: international progress and future directions. Leukemia. 2005;19(12):2025-2029. (Pubitemid 41741594)
49. Fitzgerald JB, Schoeberl B, Nielsen UB, Sorger PK. Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Biol. 2006;2(9):458-466. (Pubitemid 44266307)