Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21WAF1/Cip1-dependent mechanism independent of functional p53

Blood

Volumn 124, Issue 10, 2014, Pages 1637-1644

  Fecteau, Jessie F ^a   Corral, Laura G ^b   Ghia, Emanuela M ^a   Gaidarova, Svetlana ^b   Futalan, Diahnn ^a   Bharati, Ila Sri ^a,c   Cathers, Brian ^b   Schwaederlé, Maria ^a   Cui, Bing ^a   Lopez Girona, Antonia ^b   Messmer, Davorka ^a,d   Kipps, Thomas J ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b CELGENE CORPORATION   (United States)

^c Genoptix Inc   (United States)

^d Current affiliation Inception Sciences Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CD19 ANTIGEN; CD40 LIGAND; CD5 ANTIGEN; CEREBLON PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 1; INTERLEUKIN 10; INTERLEUKIN 4; LENALIDOMIDE; PROTEIN P21; PROTEIN P53; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; ZINC FINGER PROTEIN 1; ZINC FINGER PROTEIN 3; ANGIOGENESIS INHIBITOR; CDKN1A PROTEIN, HUMAN; CRBN PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE INHIBITOR 1A; DRUG DERIVATIVE; PEPTIDE HYDROLASE; THALIDOMIDE;

ACCESSORY CELL; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER GROWTH; CELL CYCLE G0 PHASE; CELL CYCLE G2 PHASE; CELL ISOLATION; CELL PROLIFERATION; CHRONIC LYMPHATIC LEUKEMIA; COCULTURE; CYTOSTASIS; CYTOTOXICITY; DENSITOMETRY; DRUG EFFECT; FEMALE; FIBROBLAST; GENE SILENCING; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA CELL; LOW DRUG DOSE; LYMPHOCYTE COUNT; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SHORT COURSE THERAPY; UPREGULATION; GENE EXPRESSION REGULATION; HELA CELL LINE; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL CULTURE;

ANGIOGENESIS INHIBITORS; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE INHIBITOR P21; GENE EXPRESSION REGULATION, LEUKEMIC; HELA CELLS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; PEPTIDE HYDROLASES; SIGNAL TRANSDUCTION; THALIDOMIDE; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84907047022     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-03-559591     Document Type: Article

References (42)

1. Corral LG, Haslett PA, Muller GW, et al. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999;163(1):380-386.
2. Raje N, Anderson KC. Thalidomide and immunomodulatory drugs as cancer therapy. Curr Opin Oncol. 2002;14(6):635-640.
3. Richardson P, Anderson K. Immunomodulatory analogs of thalidomide: an emerging new therapy in myeloma. J Clin Oncol. 2004;22(16):3212-3214.
4. Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010;24(Suppl 1):S13-S19.
5. Andritsos LA, Johnson AJ, Lozanski G, et al. Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J Clin Oncol. 2008;26(15):2519-2525.
6. Chanan-Khan AA, Chitta K, Ersing N, et al. Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response. Br J Haematol. 2011;155(4):457-467.
7. Riches JC, Ramsay AG, Gribben JG. Immune dysfunction in chronic lymphocytic leukemia: the role for immunotherapy. Curr Pharm Des. 2012;18(23):3389-3398.
8. Schulz A, Dürr C, Zenz T, et al. Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment. Blood. 2013;121(13):2503-2511.
9. Marriott JB, Clarke IA, Dredge K, Muller G, Stirling D, Dalgleish AG. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells. Clin Exp Immunol. 2002;130(1):75-84.
10. LeBlanc R, Hideshima T, Catley LP, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2004;103(5):1787-1790.
11. Görgün G, Holderried TA, Zahrieh D, Neuberg D, Gribben JG. Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells. J Clin Invest. 2005;115(7):1797-1805.
12. Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008;118(7):2427-2437.
13. Aue G, Njuguna N, Tian X, et al. Lenalidomide-induced upregulation of CD80 on tumor cells correlates with T-cell activation, the rapid onset of a cytokine release syndrome and leukemic cell clearance in chronic lymphocytic leukemia. Haematologica. 2009;94(9):1266-1273.
14. Lapalombella R, Andritsos L, Liu Q, et al. Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway. Blood. 2010;115(13):2619-2629.
15. Verhelle D, Corral LG, Wong K, et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007;67(2):746-755.
16. Qian Z, Zhang L, Cai Z, et al. Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leuk Res. 2011;35(3):380-386.
17. Messmer BT, Messmer D, Allen SL, et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest. 2005;115(3):755-764.
18. Kipps TJ. Chronic lymphocytic leukemia and related diseases. In: Beutler E, Lichtman MA, Coller BA, Kipps TJ, Seligsohn U, eds. Williams Hematology. New York, NY: McGraw-Hill; 2001: 1163-1194.
19. Chu P, Wierda WG, Kipps TJ. CD40 activation does not protect chronic lymphocytic leukemia B cells from apoptosis induced by cytotoxic T lymphocytes. Blood. 2000;95(12):3853-3858.
20. Granelli-Piperno A, Finkel V, Delgado E, Steinman RM. Virus replication begins in dendritic cells during the transmission of HIV-1 from mature dendritic cells to T cells. Curr Biol. 1999;9(1):21-29.
21. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993;366(6456):701-704.
22. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75(4):805-816.
23. Lopez-Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012;26(11):2326-2335.
24. Zhu YX, Braggio E, Shi CX, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118(18):4771-4779.
25. Yang Y, Shaffer AL III, Emre NC, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723-737.
26. Gandhi AK, Kang J, Havens CG, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol. 2014;164(6):811-821.
27. Krönke J, Udeshi ND, Narla A, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343(6168):301-305.
28. Lu G, Middleton RE, Sun H, et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014;343(6168):305-309.
29. Chen N, Lau H, Kong L, et al. Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol. 2007;47(12):1466-1475.
30. Arumainathan A, Kalakonda N, Pettitt AR. Lenalidomide can be highly effective in chronic lymphocytic leukaemia despite T-cell depletion and deletion of chromosome 17p. Eur J Haematol. 2011;87(4):372-375.
31. Aue G, Soto S, Valdez J, et al. Trial of pulse dosed lenalidomide in previously treated chronic lymphocytic leukemia [abstract]. Blood (ASH Annual Meeting Abstracts). 2010;116(21). Abstract 1383.
32. Sher T, Miller KC, Lawrence D, et al. Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high-risk cytogenetics. Leuk Lymphoma. 2010;51(1):85-88.
33. Escoubet-Lozach L, Lin IL, Jensen-Pergakes K, et al. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res. 2009;69(18):7347-7356.
34. Jung YS, Qian Y, Chen X. Examination of the expanding pathways for the regulation of p21 expression and activity. Cell Signal. 2010;22(7):1003-1012.
35. Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345-1350.
36. John LB, Ward AC. The Ikaros gene family: transcriptional regulators of hematopoiesis and immunity. Mol Immunol. 2011;48(9-10):1272-1278.
37. Koipally J, Renold A, Kim J, Georgopoulos K. Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes. EMBO J. 1999;18(11):3090-3100.
38. Gartel AL, Radhakrishnan SK. Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res. 2005;65(10):3980-3985.
39. Brown JR, Abramson J, Hochberg E, et al. A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL. Leukemia. 2010;24(11):1972-1975.
40. Egle A, Steurer M, Gassner F, et al. A combination of fludarabine/rituximab with escalating doses of lenalidomide in previously untreated chronic lymphocytic leukemia (CLL): the REVLIRIT CLL5 AGMT Phase I/II study, clinical and exploratory analyses of induction results [abstract]. Blood (ASH Annual Meeting Abstracts). 2011;118(21). Abstract 292.
41. Flinn IA, Schreeder MT, Wagner-Johnston N, et al. Preliminary results from a phase I/II study of fludarabine, rituximab, and lenalidomide in untreated patients with chronic lymphocytic leukemia (CLL) [abstract]. Blood ASH Annual Meeting Abstracts). 2010;116(21). Abstract 2832.
42. Strati P, Keating MJ, Wierda WG, et al. Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia. Blood. 2013;122(5):734-737.