Detection of bcr-abl gene expression at a low level in blood cells of some patients with essential thrombocythemia

Hsu, Hui‐Chi; Tan, Lin-Ya; Au, Lo‐Chun; Lee, Yuan-Ming; Lieu, Chien-Hui; Tsai, Wen‐Hui; You, Jie-Yu; Liu, Ming-Der; Ho, Chi-Kuan

doi:10.1016/j.lab.2003.10.007

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…All autopsied individuals aged 50-70 have in-situ carcinomas in their thyroid gland despite its rare diagnosis during life. There are normal individuals with the ÔPhiladelphiaÕ chromosome translocation which is found in 95% of patients with chronic myelocytic leukemia and contributes to its etiology [48]. Chronic lymphatic leukemia (CLL) clones have been described in ÔnormalÕ elderly men as well as close degree relatives of patients with CLL [49].…”

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confidence: 99%

Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis

Lee

Campbell

et al. 2004

Blood

172

152

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Tumor/host-generated thrombin (endogenous thrombin) was investigated with tumor growth and metastasis experiments in mice by the use of hirudin, a highly potent specific inhibitor of thrombin. Pretreatment with hirudin inhibited tumor implantation in nude or syngeneic mice, following subcutaneous injection of 2 human and 2 murine tumors. Hirudin induced a considerable lag period in the appearance of tumor growth, compared with phosphate-buffered saline (PBS) treatment, but had no effect on established tumor nodule growth in vivo or on tumor growth in vitro. Hirudin treatment induced central necrosis of the tumor nodule compared with no effect with PBS treatment. Greater protection was noted with longer duration of treatment. Tumor seeding into blood was examined with green fluorescent protein ( IntroductionThe association of thrombosis and cancer (platelet and fibrin deposition) is well established, 1-5 but the role that activation of the coagulation pathway plays in promoting neoplastic progression is not well defined. We and others have shown that exogenous thrombin (1 U/mL) acting through its PAR-1 receptor, is capable of enhancing tumor adhesion to platelets, 6-8 endothelial cells, 9 fibronectin, and von Willebrand factor 7 in vitro. Studies have also revealed that exogenous thrombin promotes tumor growth in vitro 10 and in vivo 6,7,11 as well as experimental (tail-vein injection) metastasis. [6][7][8]12 Exogenous thrombin is also capable of inducing angiogenesis in a chorioallantoic membrane model. 13 However, the pathophysiologic relevance of thrombin in the host, that is, the end result of endogenous generation of host thrombin during tumor growth and spontaneous metastasis, has not been examined. Indeed, the concentration of thrombin generated by a developing tumor in the plasma at the interface is unknown and uncertain. In addition, the effect of thrombin on tumor growth in vitro is biplasic (activation at Ͻ 0.5 U/mL and inhibition at higher concentration). 10 Most tumor cells have constitutively active tissue factor on their surface capable of generating thrombin in vitro. However, the host has antithrombin mechanisms capable of neutralizing this activity.An approach was therefore designed to explore the mechanism of endogenously generated thrombin with its possible effect on tumor growth, seeding, and spontaneous metastasis by employing the highly potent and specific inhibitor of thrombin, hirudin. Hirudin is twice as potent as heparin in animal thrombosis models. [14][15][16] Unlike heparin, it is capable of neutralizing thrombin bound to the tumor thrombus as well as in the plasma, 17,18 with a Ki (inhibitory constant) of 0.05 pM. 19 It has other antithrombotic properties. It is able to dissociate thrombin-platelet receptor complexes (greater affinity of hirudin for thrombin than for platelets). 20 It can displace reversibly bound Factor Xa from vascular endothelium, 20 which then becomes inactivated by plasma protease inhibitors, leading to reduced prothrombin activation. It has also been reported...

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confidence: 99%

Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis

Lee

Campbell

et al. 2004

Blood

172

152

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“…All autopsied individuals aged 50–70 have in‐situ carcinomas in their thyroid gland despite its rare diagnosis during life. There are normal individuals with the ‘Philadelphia’ chromosome translocation which is found in 95% of patients with chronic myelocytic leukemia and contributes to its etiology [48]. Chronic lymphatic leukemia (CLL) clones have been described in ‘normal’ elderly men as well as close degree relatives of patients with CLL [49].…”

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confidence: 99%

Does hypercoagulability awaken dormant tumor cells in the host?

Karpatkin

2004

Journal of Thrombosis and Haemostasis

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“…7 Our patient’s p210 transcript levels (38.2%) were relatively low at diagnosis, and this is consistent with previous reports of adult ET-like CML. 15 Some reports of adult patients with CML with thrombocythemic onset and the b3/a2 transcript variant have reported additional cytogenetic abnormalities apart from Ph chromosome; making some authors attribute the slightly poorer prognosis in these patients relative to typical CML to this finding. 16 Molecular factors influencing normal WBC counts are not clearly defined but may also result from differential kinase activity or differential activity in other motifs influencing cell adhesion.…”

Section: Discussionmentioning

confidence: 98%

A Rare Case of Pediatric Chronic Myelogenous Leukemia Presenting With Severe Thrombocytosis Without Leukocytosis

et al. 2017

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Pediatric chronic myelogenous leukemia is uncommon. We report a pediatric patient with chronic myelogenous leukemia presenting with a normal white blood cell count and no circulating immature myeloid cells. The patient presented with extreme thrombocytosis (platelet count range: 2175-3064 Â 10 9 /L) noted incidentally. No splenomegaly was found. Examination of the bone marrow aspirate revealed normal cellularity and normal myeloid: erythroid ratio with marked megakaryocytic hyperplasia. Molecular studies on the bone marrow aspirate detected both the major BCR/ABL1 p210 fusion transcript (9280 copies; p210/ABL1 ratio: 38.2%) and the minor p190 transcript (below limit of quantitation). The platelet count normalized within 2 weeks after treatment with the second-generation tyrosine kinase inhibitor dasatinib. Follow-up after 3 months revealed a 1.87 log reduction in p210 transcripts compared to diagnosis and no detectable p190 transcripts. This case highlights the need to include BCR/ABL1 fusion testing to accurately diagnose pediatric patients presenting with isolated thrombocytosis.

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Detection of bcr-abl gene expression at a low level in blood cells of some patients with essential thrombocythemia

Cited by 14 publications

References 23 publications

Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis

Role of endogenous thrombin in tumor implantation, seeding, and spontaneous metastasis

Does hypercoagulability awaken dormant tumor cells in the host?

A Rare Case of Pediatric Chronic Myelogenous Leukemia Presenting With Severe Thrombocytosis Without Leukocytosis

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