Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion

Science Translational Medicine

Volumn 9, Issue 387, 2017, Pages

  He, Shenghui ^a   Roberts, Patrick J ^b   Sorrentino, Jessica A ^b   Bisi, John E ^b   Storrie White, Hannah ^b   Tiessen, Renger G ^c   Makhuli, Karenann M ^b   Wargin, William A ^d   Tadema, Henko ^c   Van Hoogdalem, Ewoud Jan ^c   Strum, Jay C ^b   Malik, Rajesh ^b   Sharpless, Norman E ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b Research Triangle Park   (United States)

^c PRA HEALTH SCIENCES   (United States)

^d Research Triangle Park   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; DOXYCYCLINE; FLUOROURACIL; PALBOCICLIB; PEGFILGRASTIM; RIBOCICLIB; TRILACICLIB;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BLOOD CELL COUNT; BODY MASS; BONE MARROW SUPPRESSION; CANCER CHEMOTHERAPY; CELL CYCLE ARREST; CELL ISOLATION; CELL PROLIFERATION; COLONY FORMATION; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOTOXICITY; ELECTROCARDIOGRAPHY; ENZYME INHIBITION; EXHAUSTION; FEMALE; FLOW CYTOMETRY; HEADACHE; HEMATOPOIETIC STEM CELL; HUMAN; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; MALE; MOUSE; NAUSEA; NONHUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEINASE INHIBITION; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; RISK ASSESSMENT; URINALYSIS; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE MARROW CELL; C57BL MOUSE; CELL CYCLE CHECKPOINT; CYTOLOGY; DRUG EFFECTS; METABOLISM; NORMAL HUMAN;

ANIMALS; BONE MARROW CELLS; CELL CYCLE CHECKPOINTS; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE 4; CYCLIN-DEPENDENT KINASE 6; FEMALE; FLUOROURACIL; HEALTHY VOLUNTEERS; HEMATOPOIETIC STEM CELLS; HUMANS; MALE; MICE; MICE, INBRED C57BL;

EID: 85018296832     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aal3986     Document Type: Article

References (54)

1. J. Harris, D. Sengar, T. Stewart, D. Hyslop, The effect of immunosuppressive chemotherapy on immune function in patients with malignant disease. Cancer 37, 1058-1069 (1976).
2. R. V. Gardner, C. Lerner, C. M. Astle, D. E. Harrison, Assessing permanent damage to primitive hematopoietic stem cells after chemotherapy using the competitive repopulation assay. Cancer Chemother. Pharmacol. 32, 450-454 (1993).
3. P. Mauch, L. Constine, J. Greenberger, W. Knospe, J. Sullivan, J. L. Liesveld, H. J. Deeg, Hematopoietic stem cell compartment: Acute and late effects of radiation therapy and chemotherapy. Int. J. Radiat. Oncol. Biol. Phys. 31, 1319-1339 (1995).
4. R. V. Gardner, Long term hematopoietic damage after chemotherapy and cytokine. Front. Biosci. 4, e47-e57 (1999).
5. Y. Wang, V. Probin, D. Zhou, Cancer therapy-induced residual bone marrow injury: Mechanisms of induction and implication for therapy. Curr. Cancer Ther. Rev. 2, 271-279 (2006).
6. R. L. Hornung, D. L. Longo, Hematopoietic stem cell depletion by restorative growth factor regimens during repeated high-dose cyclophosphamide therapy. Blood 80, 77-83 (1992).
7. M. A. Moore, Does stem cell exhaustion result from combining hematopoietic growth factors with chemotherapy? If so, how do we prevent it? Blood 80, 3-7 (1992).
8. D. Hershman, A. I. Neugut, J. S. Jacobson, J. Wang, W.-Y. Tsai, R. McBride, C. L. Bennett, V. R. Grann, Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J. Natl. Cancer Inst. 99, 196-205 (2007).
9. G. H. Lyman, D. C. Dale, D. A. Wolff, E. Culakova, M. S. Poniewierski, N. M. Kuderer, J. Crawford, Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: A systematic review. J. Clin. Oncol. 28, 2914-2924 (2010).
10. M. Tubiana, P. Carde, E. Frindel, Ways of minimising hematopoietic damage induced by radiation and cytostatic drugs-The possible role of inhibitors. Radiother. Oncol. 29, 1-17 (1993).
11. M. V. Blagosklonny, A. B. Pardee, Exploiting cancer cell cycling for selective protection of normal cells. Cancer Res. 61, 4301-4305 (2001).
12. M. Malumbres, R. Sotillo, D. Santamaria, J. Galán, A. Cerezo, S. Ortega, P. Dubus, M. Barbacid, Mammalian cells cycle without the D-Type cyclin-dependent kinases Cdk4 and Cdk6. Cell 118, 493-504 (2004).
13. K. Kozar, M. A. Ciemerych, V. I. Rebel, H. Shigematsu, A. Zagozdzon, E. Sicinska, Y. Geng, Q. Yu, S. Bhattacharya, R. T. Bronson, K. Akashi, P. Sicinski, Mouse development and cell proliferation in the absence of D-cyclins. Cell 118, 477-491 (2004).
14. S. M. Johnson, C. D. Torrice, J. F. Bell, K. B. Monahan, Q. Jiang, Y. Wang, M. R. Ramsey, J. Jin, K.-K. Wong, L. Su, D. Zhou, N. E. Sharpless, Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J. Clin. Invest. 120, 2528-2536 (2010).
15. M. J. Garnett, E. J. Edelman, S. J. Heidorn, C. D. Greenman, A. Dastur, K. W. Lau, P. Greninger, I. R. Thompson, X. Luo, J. Soares, Q. Liu, F. Iorio, D. Surdez, L. Chen, R. J. Milano, G. R. Bignell, A. T. Tam, H. Davies, J. A. Stevenson, S. Barthorpe, S. R. Lutz, F. Kogera, K. Lawrence, A. McLaren-Douglas, X. Mitropoulos, T. Mironenko, H. Thi, L. Richardson, W. Zhou, F. Jewitt, T. Zhang, P. O'Brien, J. L. Boisvert, S. Price, W. Hur, W. Yang, X. Deng, A. Butler, H. G. Choi, J. W. Chang, J. Baselga, I. Stamenkovic, J. A. Engelman, S. V. Sharma, O. Delattre, J. Saez-Rodriguez, N. S. Gray, J. Settleman, P. A. Futreal, D. A. Haber, M. R. Stratton, S. Ramaswamy, U. McDermott, C. H. Benes, Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483, 570-575 (2012).
16. U. Asghar, A. K. Witkiewicz, N. C. Turner, E. S. Knudsen, The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov. 14, 130-146 (2015).
17. P. J. Roberts, J. E. Bisi, J. C. Strum, A. J. Combest, D. B. Darr, J. E. Usary, W. C. Zamboni, K.-K. Wong, C. M. Perou, N. E. Sharpless, Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J. Natl. Cancer Inst. 104, 476-487 (2012).
18. J. E. Bisi, J. A. Sorrentino, P. J. Roberts, F. X. Tavares, J. C. Strum, Preclinical characterization of G1T28: A novel CDK4/6 inhibitor for reduction of chemotherapy-induced myelosuppression. Mol. Cancer Ther. 15, 783-793 (2016).
19. D. B. Longley, D. P. Harkin, P. G. Johnston, 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330-338 (2003).
20. C. Lerner, D. E. Harrison, 5-Fluorouracil spares hemopoietic stem cells responsible for long-Term repopulation. Exp. Hematol. 18, 114-118 (1990).
21. D. E. Harrison, C. P. Lerner, Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil. Blood 78, 1237-1240 (1991).
22. I. Beerman, C. Bock, B. S. Garrison, Z. D. Smith, H. Gu, A. Meissner, D. J. Rossi, Proliferationdependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell 12, 413-425 (2013).
23. G. de Haan, B. Donte, C. Engel, M. Loeffler, W. Nijhof, Prophylactic pretreatment of mice with hematopoietic growth factors induces expansion of primitive cell compartments and results in protection against 5-fluorouracil-induced toxicity. Blood 87, 4581-4588 (1996).
24. T. Cheng, N. Rodrigues, H. Shen, Y.-G. Yang, D. Dombkowski, M. Sykes, D. T. Scadden, Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287, 1804-1808 (2000).
25. A. Ehninger, T. Boch, H. Medyouf, K. Mudder, G. Orend, A. Trumpp, Loss of SPARC protects hematopoietic stem cells from chemotherapy toxicity by accelerating their return to quiescence. Blood 123, 4054-4063 (2014).
26. G. J. Peters, J. Lankelma, R. M. Kok, P. Noordhuis, C. J. van Groeningen, C. L. van der Wilt, S. Meyer, H. M. Pinedo, Prolonged retention of high concentrations of 5-fluorouracil in human and murine tumors as compared with plasma. Cancer Chemother. Pharmacol. 31, 269-276 (1993).
27. K. W. Orford, D. T. Scadden, Deconstructing stem cell self-renewal: Genetic insights into cell-cycle regulation. Nat. Rev. Genet. 9, 115-128 (2008).
28. S. J. Morrison, A. M. Wandycz, K. Akashi, A. Globerson, I. L. Weissman, The aging of hematopoietic stem cells. Nat. Med. 2, 1011-1016 (1996).
29. G. de Haan, W. Nijhof, G. Van Zant, Mouse strain-dependent changes in frequency and proliferation of hematopoietic stem cells during aging: Correlation between lifespan and cycling activity. Blood 89, 1543-1550 (1997).
30. P. J. Linton, K. Dorshkind, Age-related changes in lymphocyte development and function. Nat. Immunol. 5, 133-139 (2004).
31. D. J. Rossi, D. Bryder, J. M. Zahn, H. Ahlenius, R. Sonu, A. J. Wagers, I. L. Weissman, Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc. Natl. Acad. Sci. U.S.A. 102, 9194-9199 (2005).
32. H. L. Chua, P. A. Plett, C. H. Sampson, B. P. Katz, G. W. Carnathan, T. J. MacVittie, K. Lenden, C. M. Orschell, Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys. 106, 21-38 (2014).
33. C. Li, L. Lu, J. Zhang, S. Huang, Y. Xing, M. Zhao, D. Zhou, D. Li, A. Meng, Granulocyte colony-stimulating factor exacerbates hematopoietic stem cell injury after irradiation. Cell Biosci. 5, 65 (2015).
34. L. J. Bendall, K. F. Bradstock, G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev. 25, 355-367 (2014).
35. A. V. Ergen, M. A. Goodell, Mechanisms of hematopoietic stem cell aging. Exp. Gerontol. 45, 286-290 (2010).
36. I. Beerman, W. J. Maloney, I. L. Weissmann, D. J. Rossi, Stem cells and the aging hematopoietic system. Curr. Opin. Immunol. 22, 500-506 (2010).
37. H. W. Snoeck, Aging of the hematopoietic system. Curr. Opin. Hematol. 20, 355-361 (2013).
38. A. Wilson, E. Laurenti, G. Oser, R. C. van der Wath, W. Blanco-Bose, M. Jaworski, S. Offner, C. F. Dunant, L. Eshkind, E. Bockamp, P. Lió, H. R. Macdonald, A. Trumpp, Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135, 1118-1129 (2008).
39. A. Foudi, K. Hochedlinger, D. Van Buren, J. W. Schindler, R. Jaenisch, V. Carey, H. Hock, Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat. Biotechnol. 27, 84-90 (2009).
40. C. G. Murphy, M. N. Dickler, The role of CDK4/6 inhibition in breast cancer. Oncologist 20, 483-490 (2015).
41. N. Vidula, H. S. Rugo, Cyclin-dependent kinase 4/6 inhibitors for the treatment of breast cancer: A review of preclinical and clinical data. Clin. Breast Cancer 16, 8-17 (2015).
42. R. G. Sheehan, E. P. Balaban, E. P. Frenkel, The impact of dose intensity of standard chemotherapy regimens in extensive stage small cell lung cancer. Am. J. Clin. Oncol. 16, 250-255 (1993).
43. M. M. Rampurwala, G. B. Rocque, M. E. Burkard, Update on adjuvant chemotherapy for early breast cancer. Breast Cancer 8, 125-133 (2014).
44. I. Ray-Coquard, C. Cropet, M. Van Glabbeke, C. Sebban, A. Le Cesne, I. Judson, O. Tredan, J. Verweij, P. Biron, I. Labidi, J. P. Guastalla, T. Bachelot, D. Perol, S. Chabaud, P. C. Hogendoorn, P. Cassier, A. Dufresne, J. Y. Blay; European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group, Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 69, 5383-5391 (2009).
45. J. L. Dean, C. Thangavel, A. K. McClendon, C. A. Reed, E. S. Knudsen, Therapeutic CDK4/6 inhibition in breast cancer: Key mechanisms of response and failure. Oncogene 29, 4018-4032 (2010).
46. R. S. Finn, J. Dering, D. Conklin, O. Kalous, D. J. Cohen, A. J. Desai, C. Ginther, M. Atefi, I. Chen, C. Fowst, G. Los, D. J. Slamon, 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. 11, R77 (2009).
47. M. J. Niederst, L. V. Sequist, J. T. Poirier, C. H. Mermel, E. L. Lockerman, A. R. Garcia, R. Katayama, C. Costa, K. N. Ross, T. Moran, E. Howe, L. E. Fulton, H. E. Mulvey, L. A. Bernardo, F. Mohamoud, N. Miyoshi, P. A. VanderLaan, D. B. Costa, P. A. Janne, D. R. Borger, S. Ramaswamy, T. Shioda, A. J. Iafrate, G. Getz, C.M. Rudin, M.Mino-Kenudson, J. A. Engelman, RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat. Commun. 6, 6377 (2015).
48. The Cancer Genome Atlas Network, Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 (2012).
49. B. S. Taylor, N. Schultz, H. Hieronymus, A. Gopalan, Y. Xiao, B. S. Carver, V. K. Arora, P. Kaushik, E. Cerami, B. Reva, Y. Antipin, N. Mitsiades, T. Landers, I. Dolgalev, J. E. Major, M. Wilson, N. D. Socci, A. E. Lash, A. Heguy, J. A. Eastham, H. I. Scher, V. E. Reuter, P. T. Scardino, C. Sander, C. L. Sawyers, W. L. Gerald, Integrative genomic profiling of human prostate cancer. Cancer Cell 18, 11-22 (2010).
50. The Cancer Genome Atlas Research Network, Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507, 315-322 (2014).
51. A. K. Witkiewicz, K. E. Knudsen, A. P. Dicker, E. S. Knudsen, The meaning of p16ink4a expression in tumors: Functional significance, clinical associations and future developments. Cell Cycle 10, 2497-2503 (2011).
52. P. Schraml, C. Bucher, H. Bissig, A. Nocito, P. Haas, K. Wilber, S. Seelig, J. Kononen, M. J. Mihatsch, S. Dirnhofer, G. Sauter, Cyclin E overexpression and amplification in human tumours. J. Pathol. 200, 375-382 (2003).
53. A. Salic, T. J. Mitchison, A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc. Natl. Acad. Sci. U.S.A. 105, 2415-2420 (2008).
54. S. J. Morrison, I. L. Weissman, The long-Term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1, 661-673 (1994).