Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kd inhibition through PIK3IP1

Cell Cycle

Volumn 12, Issue 12, 2013, Pages 1892-1900

  Chiron, David ^a   Martin, Peter ^a   Di Liberto, Maurizio ^a   Huang, Xiangao ^a   Ely, Scott ^a   Lannutti, Brian J ^b   Leonard, John P ^a   Mason, Christopher E ^a   Chen Kiang, Selina ^a  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b GILEAD SCIENCES INC   (United States)

Author keywords

CDK4; CDK6; GS 1101; Mantle cell lymphoma; PD 0332991; PI3Ka; PI3Kd; PIK3IP1

Indexed keywords

CYCLIN D1; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; IDELALISIB; PALBOCICLIB; PHOSPHATIDYLINOSITOL 3 KINASE GAMMA;

ARTICLE; B LYMPHOCYTE; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME INHIBITION; EX VIVO STUDY; G1 PHASE CELL CYCLE CHECKPOINT; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; LYMPHOMA CELL; MANTLE CELL LYMPHOMA; PROTEIN PHOSPHORYLATION;

EID: 84879395969     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.24928     Document Type: Article

References (45)

1. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002; 296:1655-7; PMID:12040186; http://dx.doi.org/10.1126/science.296.5573.1655 (Pubitemid 34579158)
2. Fruman DA, Rommel C. PI3Kd inhibitors in cancer: Rationale and serendipity merge in the clinic. Cancer Discov 2011; 1:562-72; PMID:22586681; http://dx.doi.org/10.1158/2159-8290.CD-11-0249
3. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, et al. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci USA 1997; 94:4330-5; PMID:9113989; http://dx.doi.org/10.1073/pnas.94.9.4330 (Pubitemid 27194241)
4. Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho RA, et al. PI3 kinase signals BCRdependent mature B cell survival. Cell 2009; 139:573-86; PMID:19879843; http://dx.doi.org/10.1016/j.cell.2009.08.041
5. Herman SE, Gordon AL, Wagner AJ, Heerema NA, Zhao W, Flynn JM, et al. Phosphatidylinositol 3-kinase-d inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 2010; 116:2078-88; PMID:20522708; http://dx.doi.org/10.1182/blood-2010-02-271171
6. Hoellenriegel J, Meadows SA, Sivina M, Wierda WG, Kantarjian H, Keating MJ, et al. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011; 118:3603-12; PMID:21803855; http://dx.doi.org/10.1182/ blood-2011-05-352492
7. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 2011; 117:591-4; PMID:20959606; http://dx.doi.org/10.1182/ blood-2010-03-275305
8. Meadows SA, Vega F, Kashishian A, Johnson D, Diehl V, Miller LL, et al. PI3Kd inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood 2012; 119:1897-900; PMID:22210877; http://dx.doi.org/ 10.1182/blood-2011-10-386763
9. Kahl BBJ, Flinn IW, et al. Clinical Safety and Activity In a Phase1 Study of CAL-101, An Isoform-Selective Inhibitor of Phosphatidylinositol 3-Kinase P110{delta}, In Patients with Relapsed or Refractory Non-Hodgkin Lymphoma. ASH Annual Meeting Abstracts 2010; 116:1777.
10. Dreyling M, Weigert O, Hiddemann W; European MCL Network. Current treatment standards and future strategies in mantle cell lymphoma. Ann Oncol 2008; 19(Suppl 4):iv41-4; PMID:18519401; http://dx.doi.org/10.1093/annonc/mdn193
11. Hernández L, Beà S, Pinyol M, Ott G, Katzenberger T, Rosenwald A, et al. CDK4 and MDM2 gene alterations mainly occur in highly proliferative and aggressive mantle cell lymphomas with wild-type INK4a/ARF locus. Cancer Res 2005; 65:2199-206; PMID:15781632; http://dx.doi.org/10.1158/ 0008-5472.CAN-04-1526 (Pubitemid 40490128)
12. Korz C, Pscherer A, Benner A, Mertens D, Schaffner C, Leupolt E, et al. Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosis-associated genes. Blood 2002; 99:4554-61; PMID:12036888; http://dx.doi.org/10.1182/blood.V99.12.4554 (Pubitemid 34627227)
13. Sherr CJ, Roberts JM. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev 1999; 13:1501-12; PMID:10385618; http://dx.doi.org/10.1101/gad.13.12.1501 (Pubitemid 29297917)
14. Determann O, Hoster E, Ott G, Wolfram Bernd H, Loddenkemper C, Leo Hansmann M, et al.; European Mantle Cell Lymphoma Network and the German Low Grade Lymphoma Study Group. Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: Results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group. Blood 2008; 111:2385-7; PMID:18077791; http://dx.doi.org/10.1182/ blood-2007-10-117010 (Pubitemid 351451450)
15. Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 2004; 3:1427-38; PMID:15542782
16. Baughn LB, Di Liberto M, Wu K, Toogood PL, Louie T, Gottschalk R, et al. A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6. Cancer Res 2006; 66:7661-7; PMID:16885367; http://dx.doi.org/10.1158/0008-5472.CAN-06-1098 (Pubitemid 44289224)
17. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 2009; 11:R77; PMID:19874578; http://dx.doi.org/10.1186/bcr2419
18. Marzec M, Kasprzycka M, Lai R, Gladden AB, Wlodarski P, Tomczak E, et al. Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity. Blood 2006; 108:1744-50; PMID:16690963; http://dx.doi.org/10.1182/blood-2006-04-016634 (Pubitemid 44316145)
19. Menu E, Garcia J, Huang X, Di Liberto M, Toogood PL, Chen I, et al. A novel therapeutic combination using PD 0332991 and bortezomib: Study in the 5T33MM myeloma model. Cancer Res 2008; 68:5519-23; PMID:18632601; http://dx.doi.org/10.1158/0008-5472.CAN-07-6404
20. Sawai CM, Freund J, Oh P, Ndiaye-Lobry D, Bretz JC, Strikoudis A, et al. Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia. Cancer Cell 2012; 22:452-65; PMID:23079656; http://dx.doi.org/10.1016/j.ccr.2012.09. 016
21. Wang L, Wang J, Blaser BW, Duchemin AM, Kusewitt DF, Liu T, et al. Pharmacologic inhibition of CDK4/6: Mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia. Blood 2007; 110:2075-83; PMID:17537993; http://dx.doi.org/10.1182/blood-2007-02-071266 (Pubitemid 47443925)
22. Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 2012; 490:116-20; PMID:22885699; http://dx.doi.org/10.1038/nature11378
23. Dean JL, McClendon AK, Hickey TE, Butler LM, Tilley WD, Witkiewicz AK, et al. Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors. Cell Cycle 2012; 11:2756-61; PMID:22767154; http://dx.doi.org/10.4161/cc.21195
24. Huang X, Di Liberto M, Jayabalan D, Liang J, Ely S, Bretz J, et al. Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4. Blood 2012; 120:1095-106; PMID:22718837; http://dx.doi.org/10.1182/blood-2012-03-415984
25. Leonard JP, LaCasce AS, Smith MR, Noy A, Chirieac LR, Rodig SJ, et al. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood 2012; 119:4597-607; PMID:22383795; http://dx.doi.org/10.1182/blood-2011-10-388298
26. CDK Inhibitor Triples PFS in Breast Cancer. Cancer Discov 2013; 3:4
27. Brazzatti JA, Klingler-Hoffmann M, Haylock-Jacobs S, Harata-Lee Y, Niu M, Higgins MD, et al. Differential roles for the p101 and p84 regulatory subunits of PI3Kgamma in tumor growth and metastasis. Oncogene 2012; 31:2350-61; PMID:21996737
28. Bousquet M, Recher C, Queleen C, Demur C, Payrastre B, Brousset P. Assessment of somatic mutations in phosphatidylinositol 3-kinase gene in human lymphoma and acute leukaemia. Br J Haematol 2005; 131:411-3; PMID:16225664; http://dx.doi.org/10.1111/j.1365-2141.2005.05784.x (Pubitemid 43899676)
29. Rudelius M, Pittaluga S, Nishizuka S, Pham TH, Fend F, Jaffe ES, et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood 2006; 108:1668-76; PMID:16645163; http://dx.doi.org/10.1182/blood-2006-04-015586 (Pubitemid 44316136)
30. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: Variations on a theme. Oncogene 2008; 27:5497-510; PMID:18794884; http://dx.doi.org/10.1038/onc. 2008.245
31. Bretz J, Garcia J, Huang X, Kang L, Zhang Y, Toellner KM, et al. Noxa mediates p18INK4c cell-cycle control of homeostasis in B cells and plasma cell precursors. Blood 2011; 117:2179-88; PMID:21163929; http://dx.doi.org/10.1182/ blood-2010-06-288027
32. Meissner B, Kridel R, Lim RS, Rogic S, Tse K, Scott DW, et al. The E3 ubiquitin ligase UBR5 is recurrently mutated in mantle cell lymphoma. Blood 2013; 121:3161-4; PMID:23407552; http://dx.doi.org/10.1182/blood-2013-01-478834
33. Dal Col J, Zancai P, Terrin L, Guidoboni M, Ponzoni M, Pavan A, et al. Distinct functional significance of Akt and mTOR constitutive activation in mantle cell lymphoma. Blood 2008; 111:5142-51; PMID:18339899; http://dx.doi.org/10.1182/blood-2007-07-103481
34. Zhu Z, He X, Johnson C, Stoops J, Eaker AE, Stoffer DS, et al. PI3K is negatively regulated by PIK3IP1, a novel p110 interacting protein. Biochem Biophys Res Commun 2007; 358:66-72; PMID:17475214; http://dx.doi.org/10.1016/j. bbrc.2007.04.096 (Pubitemid 46719081)
35. Clayton E, Bardi G, Bell SE, Chantry D, Downes CP, Gray A, et al. A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp Med 2002; 196:753-63; PMID:12235209; http://dx.doi.org/10.1084/jem.20020805
36. Iyengar S, Clear A, Bödör C, Maharaj L, Lee A, Calaminici M, et al. P110a-mediated constitutive PI3K signaling limits the efficacy of p110d-selective inhibition in mantle cell lymphoma, particularly with multiple relapse. Blood 2013; 121:2274-84; PMID:23341541; http://dx.doi.org/10.1182/ blood-2012-10-460832
37. Sander S, Calado DP, Srinivasan L, Köchert K, Zhang B, Rosolowski M, et al. Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Cancer Cell 2012; 22:167-79; PMID:22897848; http://dx.doi.org/10.1016/j.ccr. 2012.06.012
38. Sander S, Rajewsky K. Burkitt lymphomagenesis linked to MYC plus PI3K in germinal center B cells. Oncotarget 2012; 3:1066-7; PMID:23164662
39. Burger JA, Hoellenriegel J. Phosphoinositide 3'-kinase delta: Turning off BCR signaling in Chronic Lymphocytic Leukemia. Oncotarget 2011; 2:737-8; PMID:22006556
40. McClendon AK, Dean JL, Rivadeneira DB, Yu JE, Reed CA, Gao E, et al. CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy. Cell Cycle 2012; 11:2747-55; PMID:22751436; http://dx.doi.org/10.4161/cc.21127
41. He X, Zhu Z, Johnson C, Stoops J, Eaker AE, Bowen W, et al. PIK3IP1, a negative regulator of PI3K, suppresses the development of hepatocellular carcinoma. Cancer Res 2008; 68:5591-8; PMID:18632611; http://dx.doi.org/10.1158/ 0008-5472.CAN-08-0025
42. DeFrances MC, Debelius DR, Cheng J, Kane LP. Inhibition of T-cell activation by PIK3IP1. Eur J Immunol 2012; 42:2754-9; PMID:22706993; http://dx.doi.org/10.1002/eji.201141653
43. Schmidt-Strassburger U, Schips TG, Maier HJ, Kloiber K, Mannella F, Braunstein KE, et al. Expression of constitutively active FoxO3 in murine forebrain leads to a loss of neural progenitors. FASEB J 2012; 26:4990-5001; PMID:22935140; http://dx.doi.org/10.1096/fj.12-208587
44. Dickson MA, Tap WD, Keohan ML, D'Angelo SP, Gounder MM, Antonescu CR, et al. Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma. J Clin Oncol 2013; Epub Ahead of Print; PMID:23569312; http://dx.doi.org/10.1200/JCO.2012. 46.5476
45. Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res 2008; 18:1851-8; PMID:18714091; http://dx.doi.org/10.1101/gr.078212.108