Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia

  • Authors:
    • Amina Kariminia
    • Sabine M. Ivison
    • Vivian M. Leung
    • Susanna Sung
    • Nicole Couto
    • Jacob Rozmus
    • Nina Rolf
    • Aru Narendran
    • Sandra E. Dunn
    • Gregor S.D. Reid
    • Kirk R. Schultz
  • View Affiliations

  • Published online on: November 28, 2016     https://doi.org/10.3892/ol.2016.5437
  • Pages: 497-505
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Abstract

Y-box-binding protein 1 (YB-1) is a regulatory protein that is associated with drug resistance and relapse in solid tumors. As YB-1 mediates some of its activity through growth factor receptor signaling dysregulation, the present study compared the expression of YB‑1 and interleukin 7 (IL‑7) receptor α (IL‑7Rα) in pediatric B‑cell precursor (BCP) acute lymphoblastic leukemia (ALL) and normal BCP cells. The expression levels of IL‑7Rα and YB‑1 were higher in relapsed vs. diagnostic samples of primary BCP ALL; however, co‑expression was also observed in a minor BCP cell population in samples from healthy donors. Functional crosstalk between YB‑1 and IL‑7R was detected: Overexpression of YB‑1 increased surface levels of IL‑7R in B cells, and the stimulation of BCP ALL cell lines and primary samples by IL‑7 activated YB‑1 by phosphorylation at S102 in a phosphatidylinositol 3-kinase-independent and MEK1/2‑dependent manner. Targeted knockdown of YB‑1 reduced IL-7-mediated protection against rapamycin, and an inhibitor of MEK1/2 potentiated rapamycin‑mediated killing in the presence of IL‑7. These data establish a novel link between two well‑characterized pro‑survival factors in acute leukemia, and suggest that YB‑1 inhibition may represent a novel therapeutic strategy for increasing sensitivity to chemotherapy in patients with refractory acute B-cell leukemia.
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January-2017
Volume 13 Issue 1

Print ISSN: 1792-1074
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Spandidos Publications style
Kariminia A, Ivison SM, Leung VM, Sung S, Couto N, Rozmus J, Rolf N, Narendran A, Dunn SE, Reid GS, Reid GS, et al: Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia. Oncol Lett 13: 497-505, 2017
APA
Kariminia, A., Ivison, S.M., Leung, V.M., Sung, S., Couto, N., Rozmus, J. ... Schultz, K.R. (2017). Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia. Oncology Letters, 13, 497-505. https://doi.org/10.3892/ol.2016.5437
MLA
Kariminia, A., Ivison, S. M., Leung, V. M., Sung, S., Couto, N., Rozmus, J., Rolf, N., Narendran, A., Dunn, S. E., Reid, G. S., Schultz, K. R."Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia". Oncology Letters 13.1 (2017): 497-505.
Chicago
Kariminia, A., Ivison, S. M., Leung, V. M., Sung, S., Couto, N., Rozmus, J., Rolf, N., Narendran, A., Dunn, S. E., Reid, G. S., Schultz, K. R."Y-box-binding protein 1 contributes to IL-7-mediated survival signaling in B-cell precursor acute lymphoblastic leukemia". Oncology Letters 13, no. 1 (2017): 497-505. https://doi.org/10.3892/ol.2016.5437