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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2018 | Research

Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008

Authors: Helicia Paz, Eun Ji Joo, Chih-Hsing Chou, Fei Fei, Kevin H. Mayo, Hisham Abdel-Azim, Haike Ghazarian, John Groffen, Nora Heisterkamp

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Abstract

Background

Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP-ALL) cells is conferred by both intrinsic and extrinsic factors, which could be targeted to promote chemo-sensitization. Our previous studies showed that Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has both an intracellular and extracellular location, protects different subtypes of BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its expression was previously reported to be restricted to the MLL subtype of BP-ALL.

Methods and results

Here, we report that Galectin-1 is expressed at different levels in and on different subclasses of BP-ALLs. Bone marrow plasma also contains high levels of Galectin-1. PTX008 is an allosteric inhibitor which inhibits Galectin-1 but not Galectin-3-mediated agglutination. The compound reduces migration of BP-ALL cells to CXCL12 and OP9 stromal cells and inhibits fibronectin-mediated adhesion. It also affects cell cycle progression of BCP-ALL cells. PTX008 is cytostatic for BP-ALL cells even when these are co-cultured with protective stroma, and can sensitize ALL cells to vincristine chemotherapy in vitro and in mice.

Conclusions

PTX008 inhibits multiple functions that contribute to BP-ALL survival. The effects of Galectin-1 inhibition on both BP-ALL cell proliferation and migration suggest both the leukemia cells as well as the microenvironment that protects these cells may be targeted.

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Title: Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008
Authors: Helicia Paz
Eun Ji Joo
Chih-Hsing Chou
Fei Fei
Kevin H. Mayo
Hisham Abdel-Azim
Haike Ghazarian
John Groffen
Nora Heisterkamp
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-018-0721-7

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