Abstract:
:The oral bacterium, Aggregatibacter actinomycetemcomitans, produces a leukotoxin (LtxA) that is specific for white blood cells (WBCs) from humans and Old World primates by interacting with lymphocyte function antigen-1 (LFA-1) on susceptible cells. To determine if LtxA could be used as a therapeutic agent for the treatment of WBC diseases, we tested the in vitro and in vivo anti-leukemia activity of the toxin. LtxA kills human malignant WBC lines and primary leukemia cells from acute myeloid leukemia patients, but healthy peripheral blood mononuclear cells (PBMCs) are relatively resistant to LtxA-mediated cytotoxicity. Levels of LFA-1 on cell lines correlated with killing by LtxA and the toxin preferentially killed cells expressing the activated form of LFA-1. In a SCID mouse model for human leukemia, LtxA had potent therapeutic value resulting in long-term survival in LtxA-treated mice. Intravenous infusion of LtxA into a rhesus macaque resulted in a drop in WBC counts at early times post-infusion; however, red blood cells, platelets, hemoglobin and blood chemistry values remained unaffected. Thus, LtxA may be an effective and safe novel therapeutic agent for the treatment of hematologic malignancies.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Kachlany SC,Schwartz AB,Balashova NV,Hioe CE,Tuen M,Le A,Kaur M,Mei Y,Rao Jdoi
10.1016/j.leukres.2009.08.022subject
Has Abstractpub_date
2010-06-01 00:00:00pages
777-85issue
6eissn
0145-2126issn
1873-5835pii
S0145-2126(09)00429-9journal_volume
34pub_type
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pub_type: 杂志文章
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