Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Multiple myeloma gammopathies

Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation


Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. 1.

    Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017;14:417–33.

  2. 2.

    Moras M, Lefevre SD, Ostuni MA. From erythroblasts to mature red blood cells: organelle clearance in mammals. Front Physiol. 2017;8:1076.

    Article  Google Scholar 

  3. 3.

    Nguyen AT, Prado MA, Schmidt PJ, Sendamarai AK, Wilson-Grady JT, Min M, et al. UBE2O remodels the proteome during terminal erythroid differentiation. Science. 2017;357:eaan0218.

    Article  Google Scholar 

  4. 4.

    Moura PL, Hawley BR, Mankelow TJ, Griffiths RE, Dobbe JGG, Streekstra GJ, et al. Non-muscle myosin II drives vesicle loss during human reticulocyte maturation. Haematologica. 2018;103:1997–2007.

    CAS  Article  Google Scholar 

  5. 5.

    Giarratana M-C, Kobari L, Lapillonne H, Chalmers D, Kiger L, Cynober T, et al. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol. 2004;23:69–74.

    Article  Google Scholar 

  6. 6.

    Rankin EB, Wu C, Khatri R, Andersen R, Araldi E, Rankin AL, et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell. 2012;149:63–74.

    CAS  Article  Google Scholar 

  7. 7.

    Shah S, Huang X, Cheng L. Concise review: stem cell-based approaches to red blood cell production for transfusion. Stem Cells Transl Med. 2013;3:346–55.

    Article  Google Scholar 

  8. 8.

    O’Connor OA, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, et al. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin Cancer Res. 2009;15:7085–91.

    Article  Google Scholar 

  9. 9.

    Perron G, Jandaghi P, Solanki S, Safisamghabadi M, Storoz C, Karimzadeh M, et al. A general framework for interrogation of mRNA stability programs identifies RNA-binding proteins that govern cancer transcriptomes. Cell Rep. 2018;23:1639–50.

    CAS  Article  Google Scholar 

  10. 10.

    Bresson S, Tollervey D. Tailing off: PABP and CNOT generate cycles of mRNA deadenylation. Mol Cell. 2018;70:987–8.

    CAS  Article  Google Scholar 

  11. 11.

    Delforge M, Dhawan R, Robinson D, Meunier J, Regnault A, Esseltine D-L, et al. Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial. Eur J Haematol. 2012;89:16–27.

    CAS  Article  Google Scholar 

  12. 12.

    Lonial S, Waller EK, Richardson PG, Jagannath S, Orlowski RZ, Giver CR, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood. 2005;106:3777–84.

    CAS  Article  Google Scholar 

  13. 13.

    Carulli G, Marini A, Azzarà A, Lucchetti A, Petrini M. Pseudoreticulocytosis in a case of myelodysplastic syndrome. Acta Haematol. 1998;100:156–8.

    CAS  Article  Google Scholar 

  14. 14.

    Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2014;372:142–52.

    Article  Google Scholar 

  15. 15.

    Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27.

    CAS  Article  Google Scholar 

Download references


This study was supported in part by the UZ Leuven Janssen Hematology Fund and “the Luc Fraiture” Fund. We would like to acknowledge Dr Christa Maes for providing the osteoblastic cell lines and Mrs Annouschka Laenen (L-Biostat and Leuven Cancer Institute, KU Leuven, Belgium) for statistical support, Dr Francis Impens (Proteomics Expertise Center, Flemish Institute of Biotechnology, Ghent, Belgium) for processing and analyzing the LC-MS/MS data and Somersault 18:24 (Diest, Belgium) for their assistance in constructing Fig. 2c.

Author information




NK, KDK, CV and MD designed the research. NK and EH performed the research. NK obtained patient samples. DP performed bioinformatics analyses. NK wrote the manuscript. KDK, CV and MD critically reviewed the manuscript.

Corresponding author

Correspondence to Nicolas G. Kint.

Ethics declarations

Conflict of interest

NK: travel support from Celgene, Amgen and Takeda, MD: speaker’s honoraria from Amgen, Celgene, Janssen, Takeda. Other authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kint, N.G., Heylen, E., Pepe, D. et al. Carfilzomib-induced reticulocytosis in patients with multiple myeloma is caused by impaired terminal erythroid maturation. Leukemia 34, 651–655 (2020).

Download citation


Quick links