Skip to main content

Advertisement

SpringerLink
Log in

Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Autologous stem cell transplantation (ASCT) is a potentially curative therapy but requires collection of sufficient blood stem cells (PBSC). Up to 40 % of patients with multiple myeloma (MM) fail to collect an optimum number of PBSC using filgrastim only and often require costly plerixafor rescue. The nonsteroidal anti-inflammatory drug meloxicam mobilizes PBSC in mice, nonhuman primates and normal volunteers, and has the potential to attenuate mobilization-induced oxidative stress on stem cells. In a single-center study, we evaluated whether a meloxicam regimen prior to filgrastim increases collection and/or homeostasis of CD34+ cells in MM patients undergoing ASCT. Mobilization was not significantly different with meloxicam in this study; a median of 2.4 × 106 CD34+ cells/kg were collected in the first apheresis and 9.2 × 106 CD34+ cells/kg were collected overall for patients mobilized with meloxicam-filgrastim, versus 4.1 × 106 in first apheresis and 7.2 × 106/kg overall for patients mobilized with filgrastim alone. CXCR4 expression was reduced on CD34+ cells and a higher CD4+/CD8+ T-cell ratio was observed after mobilization with meloxicam-filgrastim. All patients treated with meloxicam-filgrastim underwent ASCT, with neutrophil and platelet engraftment similar to filgrastim alone. RNA sequencing of purified CD34+ cells from 22 MM patients mobilized with meloxicam-filgrastim and 10 patients mobilized with filgrastim only identified > 4,800 differentially expressed genes (FDR < 0.05). Enrichment analysis indicated significant attenuation of oxidative phosphorylation and translational activity, possibly mediated by SIRT1, suggesting meloxicam may counteract oxidative stress during PBSC collection. Our results indicate that meloxicam was a safe, low-cost supplement to filgrastim mobilization, which appeared to mitigate HSPC oxidative stress, and may represent a simple means to lessen stem cell exhaustion and enhance graft quality.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The accession number for the RNA sequencing data reported in this paper is GEO:GSE174346. The trial was registered on Clintirials.gov, [NCT02078102].

Code Availability

Not applicable.

References

  1. Attal, M., Harousseau, J. L., Stoppa, A. M., Sotto, J. J., Fuzibet, J. G., Rossi, J. F., & Bataille, R. (1996). A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. The New England Journal of Medicine, 335, 91–97

    Article  CAS  PubMed  Google Scholar 

  2. Child, J. A., Morgan, G. J., Davies, F. E., Owen, R. G., Bell, S. E., Hawkins, K., & Selby, P. J. (2003). High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. The New England Journal of Medicine, 348, 1875–1883

    Article  CAS  PubMed  Google Scholar 

  3. Palumbo, A., Bringhen, S., Petrucci, M. T., Musto, P., Rossini, F., Nunzi, M., & Boccadoro, M. (2004). Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood, 104, 3052–3057

    Article  CAS  PubMed  Google Scholar 

  4. Palumbo, A., Gay, F., Falco, P., Crippa, C., Montefusco, V., Patriarca, F., & Boccadoro, M. (2010). Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. Journal of Clinical Oncology, 28, 800–807

    Article  CAS  PubMed  Google Scholar 

  5. Bensinger, W., Appelbaum, F., Rowley, S., Storb, R., Sanders, J., Lilleby, K., & Weaver, C. (1995). Factors that influence collection and engraftment of autologous peripheral-blood stem cells. Journal of Clinical Oncology, 13, 2547–2555

    Article  CAS  PubMed  Google Scholar 

  6. Stiff, P. J., Micallef, I., Nademanee, A. P., Stadtmauer, E. A., Maziarz, R. T., Bolwell, B. J., & DiPersio, J. F. (2011). Transplanted CD34(+) cell dose is associated with long-term platelet count recovery following autologous peripheral blood stem cell transplant in patients with non-Hodgkin lymphoma or multiple myeloma. Biology of Blood and Marrow Transplantation, 17, 1146–1153

    Article  CAS  PubMed  Google Scholar 

  7. Yoon, D. H., Sohn, B. S., Jang, G., Kim, E. K., Kang, B. W., Kim, C., & Suh, C. (2009). Higher infused CD34 + hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin’s lymphoma. Transfusion, 49, 1890–1900

    Article  CAS  PubMed  Google Scholar 

  8. DiPersio, J. F. (2010). Can every patient be mobilized? Best Practice & Research. Clinical Haematology, 23, 519–523

    Article  Google Scholar 

  9. Gertz, M. A., Kumar, S. K., Lacy, M. Q., Dispenzieri, A., Hayman, S. R., Buadi, F. K., & Litzow, M. R. (2009). Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma. Bone Marrow Transplantation, 43, 619–625

    Article  CAS  PubMed  Google Scholar 

  10. Giralt, S., Stadtmauer, E. A., Harousseau, J. L., Palumbo, A., Bensinger, W., Comenzo, R. L., & Durie, B. G. (2009). International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia, 23, 1904–1912

    Article  CAS  PubMed  Google Scholar 

  11. Pulsipher, M. A., Chitphakdithai, P., Logan, B. R., Shaw, B. E., Wingard, J. R., Lazarus, H. M., & Confer, D. L. (2013). Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program. Blood, 121, 197–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. DiPersio, J. F., Micallef, I. N., Stiff, P. J., Bolwell, B. J., Maziarz, R. T., Jacobsen, E., & Calandra, G. (2009). Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma. Journal of Clinical Oncology, 27, 4767–4773

    Article  CAS  PubMed  Google Scholar 

  13. DiPersio, J. F., Stadtmauer, E. A., Nademanee, A., Micallef, I. N., Stiff, P. J., Kaufman, J. L., & Calandra, G. (2009). Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood, 113, 5720–5726

    Article  CAS  PubMed  Google Scholar 

  14. Kymes, S. M., Pusic, I., Lambert, D. L., Gregory, M., Carson, K. R., & DiPersio, J. F. (2012). Economic evaluation of plerixafor for stem cell mobilization. The American Journal of Managed Care, 18, 33–41

    PubMed  PubMed Central  Google Scholar 

  15. Woolthuis, C. M., Brouwers-Vos, A. Z., Huls, G., de Wolf, J. T., Schuringa, J. J., & Vellenga, E. (2013). Loss of quiescence and impaired function of CD34(+)/CD38(low) cells one year following autologous stem cell transplantation. Haematologica, 98, 1964–1971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aljoufi, A., Cooper, S., & Broxmeyer, H. E. (2020). Collection and processing of mobilized mouse peripheral blood at lowered oxygen tension yields enhanced numbers of hematopoietic stem cells. Stem Cell Reviews and Reports, 16, 946–953

    Article  PubMed  PubMed Central  Google Scholar 

  17. Simsek, T., Kocabas, F., Zheng, J., Deberardinis, R. J., Mahmoud, A. I., Olson, E. N., & Sadek, H. A. (2010). The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell, 7, 380–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Guo, B., Huang, X., Lee, M. R., Lee, S. A., & Broxmeyer, H. E. (2018). Antagonism of PPAR-gamma signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis. Nature Medicine, 24, 360–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liu, X., Zheng, H., Yu, W. M., Cooper, T. M., Bunting, K. D., & Qu, C. K. (2015). Maintenance of mouse hematopoietic stem cells ex vivo by reprogramming cellular metabolism. Blood, 125, 1562–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Patterson, A. M., & Pelus, L. M. (2018). Spotlight on glycolysis: a new target for cord blood expansion. Cell Stem Cell, 22, 792–793

    Article  CAS  PubMed  Google Scholar 

  21. Gentile, P., Byer, D., & Pelus, L. M. (1983). In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2. Blood, 62, 1100–1107

    Article  CAS  PubMed  Google Scholar 

  22. Gentile, P. S., & Pelus, L. M. (1987). In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of granulocyte-monocyte progenitor cell (CFU-GM) cell-cycle rate. Experimental Hematology, 15, 119–126

    CAS  PubMed  Google Scholar 

  23. Lu, L., Pelus, L. M., Piacibello, W., Moore, M. A., Hu, W., & Broxmeyer, H. E. (1987). Prostaglandin E acts at two levels to enhance colony formation in vitro by erythroid (BFU-E) progenitor cells. Experimental Hematology, 15, 765–771

    CAS  PubMed  Google Scholar 

  24. North, T. E., Goessling, W., Walkley, C. R., Lengerke, C., Kopani, K. R., Lord, A. M., & Zon, L. I. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature, 447, 1007–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pelus, L. M. (1982). Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E. The Journal of Clinical Investigation, 70, 568–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pelus, L. M., & Gentile, P. S. (1988). In vivo modulation of myelopoiesis by prostaglandin E2. III. Induction of suppressor cells in marrow and spleen capable of mediating inhibition of CFU-GM proliferation. Blood, 71, 1633–1640

    Article  CAS  PubMed  Google Scholar 

  27. Pelus, L. M. (1989). Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (colony-forming units-granulocyte, macrophage) after acute administration of recombinant human IL-1 alpha. The Journal of Immunology, 143, 4171–4179

    Article  CAS  PubMed  Google Scholar 

  28. Hoggatt, J., Singh, P., Sampath, J., & Pelus, L. M. (2009). Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood, 113, 5444–5455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hoggatt, J., & Pelus, L. M. (2010). Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking. Leukemia, 24, 1993–2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Peled, A., Petit, I., Kollet, O., Magid, M., Ponomaryov, T., Byk, T., & Lapidot, T. (1999). Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science, 283, 845–848

    Article  CAS  PubMed  Google Scholar 

  31. Pelus, L. M., Hoggatt, J., & Singh, P. (2011). Pulse exposure of haematopoietic grafts to prostaglandin E2 in vitro facilitates engraftment and recovery. Cell Proliferation, 44(Suppl 1), 22–29

    Article  PubMed  PubMed Central  Google Scholar 

  32. Patterson, A. M., Liu, L., Sampson, C. H., Plett, P. A., Li, H., Singh, P., & Pelus, L. M. (2020). A single radioprotective dose of prostaglandin E2 blocks irradiation-induced apoptotic signaling and early cycling of hematopoietic stem cells. Stem Cell Reports, 15, 358–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hoggatt, J., Mohammad, K. S., Singh, P., Hoggatt, A. F., Chitteti, B. R., Speth, J. M., & Pelus, L. M. (2013). Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature, 495, 365–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A., Blade, J., Merlini, G., Mateos, M. V., & Miguel, J. F. (2014). International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. The Lancet Oncology, 15, e538–e548

    Article  PubMed  Google Scholar 

  35. Kaplan, E. L., & Meier, P. (1958). Nonparametric estimation from incomplete observations. Journal of the American Statistical Association, 53, 457–481

    Article  Google Scholar 

  36. Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., & Gingeras, T. R. (2013). STAR: ultrafast universal RNA-seq aligner. Bioinformatics, 29, 15–21

    Article  CAS  PubMed  Google Scholar 

  37. Breese, M. R., & Liu, Y. (2013). NGSUtils: a software suite for analyzing and manipulating next-generation sequencing datasets. Bioinformatics, 29, 494–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liao, Y., Smyth, G. K., & Shi, W. (2014). featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics, 30, 923–930

    Article  CAS  PubMed  Google Scholar 

  39. Ewels, P., Magnusson, M., Lundin, S., & Kaller, M. (2016). MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics, 32, 3047–3048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. McCarthy, D. J., Chen, Y., & Smyth, G. K. (2012). Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Research, 40, 4288–4297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010). edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26, 139–140

    Article  CAS  PubMed  Google Scholar 

  42. Kramer, A., Green, J., Pollard, J., Jr., & Tugendreich, S. (2014). Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics, 30, 523–530

    Article  PubMed  Google Scholar 

  43. Kyle, R. A., & Rajkumar, S. V. (2009). Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia, 23, 3–9

    Article  CAS  PubMed  Google Scholar 

  44. Singh, C. K., Chhabra, G., Ndiaye, M. A., Garcia-Peterson, L. M., Mack, N. J., & Ahmad, N. (2018). The role of sirtuins in antioxidant and redox signaling. Antioxidants & Redox Signaling, 28, 643–661

    Article  CAS  Google Scholar 

  45. Sarbassov, D. D., Ali, S. M., Kim, D. H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., & Sabatini, D. M. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Current Biology, 14, 1296–1302

    Article  CAS  PubMed  Google Scholar 

  46. Ruiz-Perez, M. V., Henley, A. B., & Arsenian-Henriksson, M. (2017). The MYCN Protein in Health and Disease. Genes (Basel), 8[4], 113 (27 pages)

  47. Kawano, Y., Fukui, C., Shinohara, M., Wakahashi, K., Ishii, S., Suzuki, T., & Katayama, Y. (2017). G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE2. Blood, 129, 587–597

    Article  CAS  PubMed  Google Scholar 

  48. Jeker, B., Novak, U., Mansouri, T. B., Baerlocher, G. M., Seipel, K., Mueller, B. U., & Pabst, T. (2018). NSAID treatment with meloxicam enhances peripheral stem cell mobilization in myeloma. Bone Marrow Transplantation, 53, 175–179

    Article  CAS  PubMed  Google Scholar 

  49. Jung, S. H., Yang, D. H., Ahn, J. S., Kim, Y. K., Kim, H. J., & Lee, J. J. (2014). Advanced lytic lesion is a poor mobilization factor in peripheral blood stem cell collection in patients with multiple myeloma. Journal of Clinical Apheresis, 29[6], 305–310

    Article  Google Scholar 

  50. Hoggatt, J., & Pelus, L. M. (2011). Many mechanisms mediating mobilization: an alliterative review. Current Opinion in Hematology, 18, 231–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hoggatt, J., Speth, J. M., & Pelus, L. M. (2013). Concise review: Sowing the seeds of a fruitful harvest: hematopoietic stem cell mobilization. Stem Cells, 31, 2599–2606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lapidot, T., & Petit, I. (2002). Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Experimental Hematology, 30, 973–981

    Article  CAS  PubMed  Google Scholar 

  53. Singh, P., Hoggatt, J., Kamocka, M. M., Mohammad, K. S., Saunders, M. R., Li, H., & Pelus, L. M. (2017). Neuropeptide Y regulates a vascular gateway for hematopoietic stem and progenitor cells. The Journal of Clinical Investigation, 127, 4527–4540

    Article  PubMed  PubMed Central  Google Scholar 

  54. Fruehauf, S., & Tricot, G. (2010). Comparison of unmobilized and mobilized graft characteristics and the implications of cell subsets on autologous and allogeneic transplantation outcomes. Biology of Blood and Marrow Transplantation, 16, 1629–1648

    Article  PubMed  Google Scholar 

  55. Devine, S. M., Vij, R., Rettig, M., Todt, L., McGlauchlen, K., Fisher, N., & DiPersio, J. F. (2008). Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood, 112, 990–998

    Article  CAS  PubMed  Google Scholar 

  56. Fruehauf, S., Veldwijk, M. R., Seeger, T., Schubert, M., Laufs, S., Topaly, J., & Calandra, G. (2009). A combination of granulocyte-colony-stimulating factor (G-CSF) and plerixafor mobilizes more primitive peripheral blood progenitor cells than G-CSF alone: results of a European phase II study. Cytotherapy, 11, 992–1001

    Article  CAS  PubMed  Google Scholar 

  57. Hoggatt, J., & Pelus, L. M. (2012). Hematopoietic stem cell mobilization with agents other than G-CSF. Methods in Molecular Biology, 904, 49–67

    CAS  PubMed  Google Scholar 

  58. Karpova, D., Rettig, M. P., Ritchey, J., Cancilla, D., Christ, S., Gehrs, L., & DiPersio, J. F. (2019). Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells. The Journal of Clinical Investigation, 129, 2745–2759

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hoggatt, J., Singh, P., Tate, T. A., Chou, B. K., Datari, S. R., Fukuda, S., & Pelus, L. M. (2018). Rapid mobilization reveals a highly engraftable hematopoietic stem cell. Cell, 172, 191–204

    Article  CAS  PubMed  Google Scholar 

  60. Kohli, L., & Passegue, E. (2014). Surviving change: the metabolic journey of hematopoietic stem cells. Trends in Cell Biology, 24, 479–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Takubo, K., Nagamatsu, G., Kobayashi, C. I., Nakamura-Ishizu, A., Kobayashi, H., Ikeda, E., & Suda, T. (2013). Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell, 12, 49–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mantel, C. R., O’Leary, H. A., Chitteti, B. R., Huang, X., Cooper, S., Hangoc, G., & Broxmeyer, H. E. (2015). Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell, 161, 1553–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pelus, L. M., & Broxmeyer, H. E. (2018). Peripheral blood stem cell mobilization; a look ahead. Current Stem Cell Reports, 4, 273–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li, L., & Bhatia, R. (2015). Role of SIRT1 in the growth and regulation of normal hematopoietic and leukemia stem cells. Current Opinion in Hematology, 22, 324–329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tang, F., Wu, Q., Ikenoue, T., Guan, K. L., Liu, Y., & Zheng, P. (2012). A critical role for Rictor in T lymphopoiesis. The Journal of Immunology, 189, 1850–1857

    Article  CAS  PubMed  Google Scholar 

  66. Zhang, Y., Hu, T., Hua, C., Gu, J., Zhang, L., Hao, S. … Yuan, W. (2014). Rictor is required for early B cell development in bone marrow. PLoS One 9, e103970

  67. Lee, D., Sykes, S. M., Kalaitzidis, D., Lane, A. A., Kfoury, Y., Raaijmakers, M. H., & Scadden, D. T. (2014). Transmembrane inhibitor of RICTOR/mTORC2 in hematopoietic progenitors. Stem Cell Reports, 3, 832–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Magee, J. A., Ikenoue, T., Nakada, D., Lee, J. Y., Guan, K. L., & Morrison, S. J. (2012). Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression. Cell Stem Cell, 11, 415–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wang, W. L., Sun, X. L., Wang, L., Mu, X. H., & Yuan, W. P. (2019). [Role of Rictor in Hematopoietic Stem Cells during Fetal Liver Hematopoiesis]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 27, 600–605

    PubMed  Google Scholar 

  70. King, B., Boccalatte, F., Moran-Crusio, K., Wolf, E., Wang, J., Kayembe, C., & Aifantis, I. (2016). The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells. Natural Immunity, 17, 1312–1321

    Article  CAS  Google Scholar 

  71. Wan, B., Zhou, Y. B., Zhang, X., Zhu, H., Huo, K., & Han, Z. G. (2008). hOLFML1, a novel secreted glycoprotein, enhances the proliferation of human cancer cell lines in vitro. FEBS Letters, 582, 3185–3192

    Article  CAS  PubMed  Google Scholar 

  72. Samara, P., Karachaliou, C. E., Ioannou, K., Papaioannou, N. E., Voutsas, I. F., Zikos, C., & Voelter, W. (2017). Prothymosin alpha: an alarmin and more. Current Medicinal Chemistry, 24, 1747–1760

    Article  CAS  PubMed  Google Scholar 

  73. Valk, P., Verbakel, S., Vankan, Y., Hol, S., Mancham, S., Ploemacher, R., & Delwel, R. (1997). Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood, 90, 1448–1457

    Article  CAS  PubMed  Google Scholar 

  74. Okubo, Y., Kasamatsu, A., Yamatoji, M., Fushimi, K., Ishigami, T., Shimizu, T., & Uzawa, K. (2018). Diacylglycerol lipase alpha promotes tumorigenesis in oral cancer by cell-cycle progression. Experimental Cell Research, 367, 112–118

    Article  CAS  PubMed  Google Scholar 

  75. Jiang, S., Zagozdzon, R., Jorda, M. A., Parmar, K., Fu, Y., Williams, J. S., & Avraham, H. K. (2010). Endocannabinoids are expressed in bone marrow stromal niches and play a role in interactions of hematopoietic stem and progenitor cells with the bone marrow microenvironment. The Journal of Biological Chemistry, 285, 35471–35478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jiang, S., Alberich-Jorda, M., Zagozdzon, R., Parmar, K., Fu, Y., Mauch, P., & Avraham, H. K. (2011). Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization. Blood, 117, 827–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jiang, S., Fu, Y., Williams, J., Wood, J., Pandarinathan, L., Avraham, S., & Avraham, H. K. (2007). Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells. PLoS.One, 2, e641

    Article  PubMed  PubMed Central  Google Scholar 

  78. Greipp, P. R., San, M. J., Durie, B. G., Crowley, J. J., Barlogie, B., Blade, J., & Westin, J. (2005). International staging system for multiple myeloma. Journal of Clinical Oncology, 23, 3412–3420

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by grant CA182947 (SSF, LMP) from the National Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, 980 West Walnut St, Indianapolis, IN, 46202, USA

    Andrea M. Patterson, Shuhong Zhang, Pratibha Singh, Sherif S. Farag & Louis M. Pelus

  2. Department of Microbiology & Immunology, Indiana University School of Medicine, 950 West Walnut St, Indianapolis, IN, 46202, USA

    Andrea M. Patterson, Liqiong Liu, Hongge Li, Pratibha Singh & Louis M. Pelus

  3. Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 46202, Indianapolis, IN, USA

    Yunlong Liu

  4. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Yunlong Liu

Authors
  1. Andrea M. Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liqiong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongge Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pratibha Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunlong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sherif S. Farag
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Louis M. Pelus
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made substantial contributions to the study. SSF and LMP conceived the studies and designed the clinical trial. AMP, SZ, LL, HL, PS, YL and LMP performed experiments. AMP, SSF and LMP wrote the paper.

Corresponding authors

Correspondence to Sherif S. Farag or Louis M. Pelus.

Ethics declarations

Conflicts of Interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethics Approval

The clinical trial was approved by the Institutional Review Board of Indiana University. Investigative use of patient samples was approved by the IUPUI/Clarian Institutional Review Board and the Indiana University Institutional Biosafety Committee.

Consent to Participate

IRB approved; all patients gave written informed consent.

Consent for Publication

All patients gave written informed consent.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(PDF 25 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patterson, A.M., Zhang, S., Liu, L. et al. Meloxicam with Filgrastim may Reduce Oxidative Stress in Hematopoietic Progenitor Cells during Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Multiple Myeloma. Stem Cell Rev and Rep 17, 2124–2138 (2021). https://doi.org/10.1007/s12015-021-10259-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-021-10259-y

Keywords

Search

Navigation