Leukemic target susceptibility to natural killer cytotoxicity: Relationship with BCR-ABL expression

Frédéric Baron, Ali G. Turhan, Julien Giron-Michel, Bruno Azzarone, Mohamed Bentires-Alj, Vincent Bours, Jean Henri Bourhis, Salem Chouaib, Anne Caignard

Research output: Contribution to journalArticle

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Abstract

Chronic myeloid leukemia is a clonal myeloproliferative expansion of transformed primitive hematopoietic progenitor cells characterized by high-level expression of BCR-ABL chimeric gene, which induces growth factor independence. However, the influence of BCR-ABL expression on cellmediated cytotoxicity is poorly understood. In the present study, we asked whether BCR-ABL expression interferes with leukemic target sensitivity to natural killer (NK) cell cytolysis. Our approach was based on the use of 2 BCR-ABL transfectants of the pluripotent hematopoietic cell line UT-7 expressing low (UT-7/E8, UT-7/G6) and high (UT-7/9) levels of BCR-ABL. As effector cells, we used CD56bright, CD16-, CD2- NK cells differentiated in vitro from CD34 cord blood progenitors. We demonstrated that BCR-ABL transfectants UT-7/9 were lysed by NK cells with a higher efficiency than parental and low UT-7/E8.1 and UT-7/G6 transfectants. This enhanced susceptibility to lysis correlated with an increase in expression of intercellular adhesion molecule 1 (ICAM-1) by target cells. Treatment of UT-7/9 cells by STI571 (a specific inhibitor of the abl kinase) resulted in a decrease in NK susceptibility to lysis and ICAM-1 down-regulation in target cells. Furthermore, the constitutive activation of nuclear factor-κB (NF-κB) detected in BCR-ABL transfectant UT-7/9, was significantly attenuated when cells were treated by STI571. Interestingly, inhibition of NF-κB activation by BAY11-67082 (a specific NF-κB inhibitor) resulted in down-regulation of ICAM-1 expression and a subsequent decrease in NK-induced killing of UT-7/9 transfectants. Our results show that oncogenic transformation by BCR-ABL may increase susceptibility of leukemic progenitors to NK cell cytotoxicity by a mechanism involving overexpression of ICAM-1 as a consequence of NF-κB activation.

Original languageEnglish
Pages (from-to)2107-2113
Number of pages7
JournalBlood
Volume99
Issue number6
DOIs
Publication statusPublished - Mar 15 2002

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Intercellular Adhesion Molecule-1
Cytotoxicity
Natural Killer Cells
Chemical activation
Down-Regulation
Intercellular Signaling Peptides and Proteins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematopoietic Stem Cells
Blood
Fetal Blood
Phosphotransferases
Genes
Cells
Cell Line
Imatinib Mesylate

ASJC Scopus subject areas

  • Hematology

Cite this

Baron, F., Turhan, A. G., Giron-Michel, J., Azzarone, B., Bentires-Alj, M., Bours, V., ... Caignard, A. (2002). Leukemic target susceptibility to natural killer cytotoxicity: Relationship with BCR-ABL expression. Blood, 99(6), 2107-2113. https://doi.org/10.1182/blood.V99.6.2107

Leukemic target susceptibility to natural killer cytotoxicity : Relationship with BCR-ABL expression. / Baron, Frédéric; Turhan, Ali G.; Giron-Michel, Julien; Azzarone, Bruno; Bentires-Alj, Mohamed; Bours, Vincent; Bourhis, Jean Henri; Chouaib, Salem; Caignard, Anne.

In: Blood, Vol. 99, No. 6, 15.03.2002, p. 2107-2113.

Research output: Contribution to journalArticle

Baron, F, Turhan, AG, Giron-Michel, J, Azzarone, B, Bentires-Alj, M, Bours, V, Bourhis, JH, Chouaib, S & Caignard, A 2002, 'Leukemic target susceptibility to natural killer cytotoxicity: Relationship with BCR-ABL expression', Blood, vol. 99, no. 6, pp. 2107-2113. https://doi.org/10.1182/blood.V99.6.2107
Baron F, Turhan AG, Giron-Michel J, Azzarone B, Bentires-Alj M, Bours V et al. Leukemic target susceptibility to natural killer cytotoxicity: Relationship with BCR-ABL expression. Blood. 2002 Mar 15;99(6):2107-2113. https://doi.org/10.1182/blood.V99.6.2107
Baron, Frédéric ; Turhan, Ali G. ; Giron-Michel, Julien ; Azzarone, Bruno ; Bentires-Alj, Mohamed ; Bours, Vincent ; Bourhis, Jean Henri ; Chouaib, Salem ; Caignard, Anne. / Leukemic target susceptibility to natural killer cytotoxicity : Relationship with BCR-ABL expression. In: Blood. 2002 ; Vol. 99, No. 6. pp. 2107-2113.
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