Open Access

Support of acute lymphoblastic leukemia cells by nonmalignant bone marrow stromal cells

  • Authors:
    • Sana Usmani
    • Urmila Sivagnanalingam
    • Olena Tkachenko
    • Leti Nunez
    • Jessica C. Shand
    • Craig A. Mullen
  • View Affiliations

  • Published online on: March 22, 2019     https://doi.org/10.3892/ol.2019.10188
  • Pages: 5039-5049
  • Copyright: © Usmani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present report describes work examining the manner in which nonmalignant bone marrow stromal cells prevent acute lymphoblastic leukemia (ALL) cell death. The initial focus was on the role of stromal cell‑derived C‑X‑C motif chemokine 12 (CXCL12). Interference with CXCL12 production by stroma or blockade of its interactions with ALL by plerixafor did increase ALL cell death and in sensitive ALLs there was synergistic effect with conventional chemotherapy drugs. However, in contrast to most reports, there was considerable heterogeneity regarding the effect between 7 unique primary ALLs, with several exhibiting no sensitivity to CXCL12 blockade. The diversity in effect was not explained by differences in the expression of ALL cell surface receptors for CXCL12. The modest and variable effects of interference with CXCL12 on ALL led to the assessment of gene expression profiles of stromal cells and ALL cells. Gene set enrichment analysis identified pathways associated with metabolism and redox reactions as potentially important in the stromal cell: leukemia cell interaction. Exploratory imaging studies demonstrated bidirectional transfer of intracellular calcien‑labelled molecules and also bidirectional transfer of mitochondria between stromal cells and ALL cells, providing potential means of metabolic interdependence of stromal cells and ALL cells.
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June-2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Usmani, S., Sivagnanalingam, U., Tkachenko, O., Nunez, L., Shand, J.C., & Mullen, C.A. (2019). Support of acute lymphoblastic leukemia cells by nonmalignant bone marrow stromal cells. Oncology Letters, 17, 5039-5049. https://doi.org/10.3892/ol.2019.10188
MLA
Usmani, S., Sivagnanalingam, U., Tkachenko, O., Nunez, L., Shand, J. C., Mullen, C. A."Support of acute lymphoblastic leukemia cells by nonmalignant bone marrow stromal cells". Oncology Letters 17.6 (2019): 5039-5049.
Chicago
Usmani, S., Sivagnanalingam, U., Tkachenko, O., Nunez, L., Shand, J. C., Mullen, C. A."Support of acute lymphoblastic leukemia cells by nonmalignant bone marrow stromal cells". Oncology Letters 17, no. 6 (2019): 5039-5049. https://doi.org/10.3892/ol.2019.10188