Vincristine but not imatinib could suppress mesenchymal niche's support to lymphoid leukemic cells

Bone marrow mesenchymal stromal cells (MSCs) can rescue acute lymphoblastic leukemia (ALL) cells from l-asparaginase by replenishing the depleted asparagine. As both vincristine (VCR) and imatinib mesylate (IM) can inhibit MSCs' proliferation, we hypothesized that these drugs might reduce the n...

Full description

Saved in:
Bibliographic Details
Published in:Leukemia & lymphoma 2010-03, Vol.51 (3), p.515-522
Main Authors: Fung, Kwong-Lam, Liang, Raymond Hin-Suen, Chan, Godfrey Chi-Fung
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Asparaginase - metabolism
Benzamides
bone marrow
Bone Marrow Cells - cytology
Coculture Techniques
Drug Screening Assays, Antitumor
Humans
Imatinib Mesylate
Inhibitory Concentration 50
Leukemia, Lymphoid - drug therapy
Leukemia, Lymphoid - pathology
lymphoid leukemic cells
Mesenchymal Stem Cells - cytology
mesenchymal stromal cell
Mesoderm - metabolism
Models, Biological
Piperazines - pharmacology
Pyrimidines - pharmacology
Stromal Cells - metabolism
stromal suppression
Tetrazolium Salts - pharmacology
Vincristine
Vincristine - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bone marrow mesenchymal stromal cells (MSCs) can rescue acute lymphoblastic leukemia (ALL) cells from l-asparaginase by replenishing the depleted asparagine. As both vincristine (VCR) and imatinib mesylate (IM) can inhibit MSCs' proliferation, we hypothesized that these drugs might reduce the niche support of MSCs to ALL cells. As a consequence, they can help to re-establish the cytotoxic potential of l-asparaginase on ALL cells even under MSCs support. In our study, pre-treating human MSCs with VCR but not IM, markedly reduced the protective capacity of MSCs. Furthermore, differential rescue effects were observed during addition of exogenous l-asparagine to co-culture with or without VCR pre-treatment. This supported the postulation that VCR could suppress the protective effect of MSCs to ALL cells by suppressing l-asparagine secretion. Our results suggested that the combined VCR and l-asparaginase treatment in ALL were synergistic and VCR can serve as an effective agent in suppressing the leukemic marrow microenvironment.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428190903406798