2012
DOI: 10.1182/blood-2011-04-347187
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Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia

Abstract: 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… Show more

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Cited by 20 publications
(11 citation statements)
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“…Activation of coagulation and secondary activation of fibrinolysis are likely to occur continuously and simultaneously throughout circulation (20,24,34). The activation of coagulation is most likely associated with the leukemic cells circulating in the blood, which may contain procoagulants, and the content of these substances depends on the leukemia subtype (35,36). These substances may be released into the blood from disintegrating cells during relapse.…”
Section: Discussionmentioning
confidence: 99%
“…Activation of coagulation and secondary activation of fibrinolysis are likely to occur continuously and simultaneously throughout circulation (20,24,34). The activation of coagulation is most likely associated with the leukemic cells circulating in the blood, which may contain procoagulants, and the content of these substances depends on the leukemia subtype (35,36). These substances may be released into the blood from disintegrating cells during relapse.…”
Section: Discussionmentioning
confidence: 99%
“…78 Interestingly, induction of diet-induced hyperhomocysteinemia in a mouse model of APL (hCG-PML-RARα mice) reversed hyperfibrinolysis, thus reinforcing the relevance of A2 to APL in vivo and suggesting a potentially novel therapeutic approach to APL. 82…”
Section: Hyperfibrinolysis and Hemorrhagementioning
confidence: 99%
“…Only prothrombin time, activated partial thromboplastin time and fibrinogen levels were routinely evaluated in the protocol and no significant difference was detected between patients with low and high KMT2E transcript levels. This is not surprising, considering the complexity of pathogenesis of coagulopathy associated with APL (Kwaan & Rego, ; Jacomo et al , ). The fact that only Brazilian patients with APL were analysed here did not represent a bias because no significant difference in treatment outcome was detected among the four participating countries (Rego et al , ).…”
Section: Discussionmentioning
confidence: 88%