CXCR7 is highly expressed in acute lymphoblastic leukemia and potentiates CXCR4 response to CXCL12

PLoS One. 2014 Jan 31;9(1):e85926. doi: 10.1371/journal.pone.0085926. eCollection 2014.

Abstract

Recently, a novel CXCL12-binding receptor, has been identified. This CXCL12-binding receptor commonly known as CXCR7 (CXC chemokine receptor 7), has lately, based on a novel nomenclature, has received the name ACKR3 (atypical chemokine receptor 3). In this study, we aimed to investigate the expression of CXCR7 in leukemic cells, as well as its participation in CXCL12 response. Interesting, we clearly demonstrated that CXCR7 is highly expressed in acute lymphoid leukemic cells compared with myeloid or normal hematopoietic cells and that CXCR7 contributed to T-acute lymphoid leukemic cell migration induced by CXCL12. Moreover, we showed that the cellular location of CXCR7 varied among T-lymphoid cells and this finding may be related to their migration capacity. Finally, we hypothesized that CXCR7 potentiates CXCR4 response and may contribute to the maintenance of leukemia by initiating cell recruitment to bone marrow niches that were once occupied by normal hematopoietic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Bone Marrow / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Chemokine CXCL12 / pharmacology*
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Leukemic / drug effects
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • RNA Interference
  • Receptors, CXCR / blood
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism*
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • U937 Cells
  • Young Adult

Substances

  • ACKR3 protein, human
  • Chemokine CXCL12
  • Heterocyclic Compounds
  • Receptors, CXCR
  • Receptors, CXCR4
  • plerixafor

Grant support

This study was funded by grants from Aperfeiçoamento Pessoal de Nível Superior (CAPES). The authors also thank CNPq, FAPESP, and INCT-Sangue for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.