Selective strong synergism of Ruxolitinib and second generation tyrosine kinase inhibitors to overcome bone marrow stroma related drug resistance in chronic myelogenous leukemia

Concetta Quintarelli, Biagio De Angelis, Santa Errichiello, Simona Caruso, Nicola Esposito, Irene Colavita, Maddalena Raia, Simona Pagliuca, Novella Pugliese, Antonio M. Risitano, Marco Picardi, Luigia Luciano, Giuseppe Saglio, Giovanni Martinelli, Fabrizio Pane

Research output: Contribution to journalArticle

Abstract

The IC50 of TKIs is significantly increased when BCR-ABL+ K562 cell line is cultured in stroma conditioned media produced by BM mesenchymal cells. In particular, while the Imatinib IC50 in the stromal co-cultures was well above the in vivo through levels of the drug, the IC50s of second generation TKIs were still below their through levels. Moreover, we provide a formal comparison of the synergy between first and second generation TKIs with the JAK inhibitor Ruxolitinib to overcome BM stroma related TKI resistance. Taken together, our data provide a rationale for the therapeutic combination of TKIs and Ruxolitinib with the aim to eradicate primary BCR-ABL+ cells homed in BM niches.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalLeukemia Research
Volume38
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • BM microenvironment
  • Chronic myelogenous leukemia
  • Resistance
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology
  • Medicine(all)

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  • Cite this

    Quintarelli, C., De Angelis, B., Errichiello, S., Caruso, S., Esposito, N., Colavita, I., Raia, M., Pagliuca, S., Pugliese, N., Risitano, A. M., Picardi, M., Luciano, L., Saglio, G., Martinelli, G., & Pane, F. (2014). Selective strong synergism of Ruxolitinib and second generation tyrosine kinase inhibitors to overcome bone marrow stroma related drug resistance in chronic myelogenous leukemia. Leukemia Research, 38(2), 236-242. https://doi.org/10.1016/j.leukres.2013.11.006