Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia
dc.contributor.author | Jácomo, Rafael H | |
dc.contributor.author | Santana-Lemos, Barbara A | |
dc.contributor.author | Lima, Ana Silvia G | |
dc.contributor.author | Assis, Patricia A | |
dc.contributor.author | Lange, Ana Paula A | |
dc.contributor.author | Figueiredo-Pontes, Lorena L | |
dc.contributor.author | Oliveira, Luciana O | |
dc.contributor.author | Bassi, Sarah C | |
dc.contributor.author | Benício, Mariana TL | |
dc.contributor.author | Baggio, Márcia S | |
dc.contributor.author | Garcia, Aglair B | |
dc.contributor.author | Falcão, Roberto P | |
dc.contributor.author | Rego, Eduardo M | |
dc.date.accessioned | 2023-07-06T16:16:53Z | |
dc.date.available | 2023-07-06T16:16:53Z | |
dc.date.issued | 2012-07-05 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.issn | 1528-0020 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/177162 | |
dc.description.abstract | <jats:title>Abstract</jats:title><jats:p>Increased fibrinolysis is an important component of acute promyelocytic leukemia (APL) bleeding diathesis. APL blasts overexpress annexin II (ANXII), a receptor for tissue plasminogen activator (tPA), and plasminogen, thereby increasing plasmin generation. Previous studies suggested that ANXII plays a pivotal role in APL coagulopathy. ANXII binding to tPA can be inhibited by homocysteine and hyperhomocysteinemia can be induced by L-methionine supplementation. In the present study, we used an APL mouse model to study ANXII function and the effects of hyperhomocysteinemia in vivo. Leukemic cells expressed higher ANXII and tPA plasma levels (11.95 ng/mL in leukemic vs 10.74 ng/mL in wild-type; P = .004). In leukemic mice, administration of L-methionine significantly increased homocysteine levels (49.0 μmol/mL and < 6.0 μmol/mL in the treated and nontreated groups, respectively) and reduced tPA levels to baseline concentrations. The latter were also decreased after infusion of the LCKLSL peptide, a competitor for the ANXII tPA–binding site (11.07 ng/mL; P = .001). We also expressed and purified the p36 component of ANXII in Pichia methanolica. The infusion of p36 in wild-type mice increased tPA and thrombin-antithrombin levels, and the latter was reversed by L-methionine administration. The results of the present study demonstrate the relevance of ANXII in vivo and suggest that methionine-induced hyperhomocysteinemia may reverse hyperfibrinolysis in APL.</jats:p> | |
dc.language | en | |
dc.publisher | American Society of Hematology | |
dc.title | Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia | |
dc.type | Article | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/177162/2/2012:07_Jacome RH, et al. Blood.pdf | |
dc.identifier.doi | 10.1182/blood-2011-04-347187 | |
dc.identifier.doi | https://dx.doi.org/10.7302/7896 | |
dc.identifier.source | Blood | |
dc.description.version | Published version | |
dc.date.updated | 2023-07-06T16:16:51Z | |
dc.description.filedescription | Description of 2012:07_Jacome RH, et al. Blood.pdf : Published version | |
dc.identifier.volume | 120 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | 207 | |
dc.identifier.endpage | 213 | |
dc.identifier.name-orcid | Jácomo, Rafael H | |
dc.identifier.name-orcid | Santana-Lemos, Barbara A | |
dc.identifier.name-orcid | Lima, Ana Silvia G | |
dc.identifier.name-orcid | Assis, Patricia A | |
dc.identifier.name-orcid | Lange, Ana Paula A | |
dc.identifier.name-orcid | Figueiredo-Pontes, Lorena L | |
dc.identifier.name-orcid | Oliveira, Luciana O | |
dc.identifier.name-orcid | Bassi, Sarah C | |
dc.identifier.name-orcid | Benício, Mariana TL | |
dc.identifier.name-orcid | Baggio, Márcia S | |
dc.identifier.name-orcid | Garcia, Aglair B | |
dc.identifier.name-orcid | Falcão, Roberto P | |
dc.identifier.name-orcid | Rego, Eduardo M | |
dc.working.doi | 10.7302/7896 | en |
dc.owningcollname | Pathology, Department of |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.