KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406)

Peter, Barbara; Hadzijusufovic, Emir; Blatt, Katharina; Gleixner, Karoline V.; Pickl, Winfried F.; Thaiwong, Tuddow; Yuzbasiyan‐Gurkan, Vilma; Willmann, Michael; Valent, Peter

doi:10.1016/j.exphem.2010.05.004

Cited by 11 publications

(7 citation statements)

References 53 publications

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“…The results are consistent with previous reports that another canine MCT cell line, C2, which had ITD of juxtamembrane domain in KIT was sensitive to the several TKIs such as imatinib, midostaurin, nilotinib, dasatinib, toceranib, and bafetinib (Liao et al, 2002;Gleixner et al, 2007;Peter et al, 2010). According to some clinical studies, 100% and 60% of canine MCT case harboring ITD of juxtamembrane domain had beneficial response (complete or partial remission) to imatinib and toceranib, respectively (Isotani et al, 2008;London et al, 2009).…”

Section: Discussionsupporting

confidence: 91%

Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses

Takeuchi

Fujino

Fukushima

et al. 2011

Vet Pharm & Therapeutics

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Tyrosine kinase inhibitors (TKIs) can be important in the treatment of canine mast cell tumor (cMCT). Meanwhile, some TKIs have been identified as substrates for ABCB1. The inhibitory effect of four TKIs (axitinib, imatinib, masitinib, and vatalanib) for proliferation and phosphorylation of c-Kit receptor as well as the expression and function of ABCB1 were investigated in three cMCT cell lines (HRMC, VIMC1, and CMMC1). The IC(50) values of the TKIs in HRMC, the only cell line with wild-type KIT, were clearly higher than those in CMMC1 and VIMC1. In HRMC and CMMC1, both the growth and phosphorylation of c-Kit receptor were suppressed proportionally by the TKIs. VIMC1 required higher concentrations for the inhibition of c-Kit receptor phosphorylation than those in cell growth. The treatment with cyclosporine increased the effects of the TKIs on VIMC1 since ABCB1 was expressed in VIMC1. The results indicated that cMCT cell lines harboring wild-type KIT had lower sensitivity to TKIs. The growth of VIMC1 was seemingly reduced by TKIs through the inhibition of other tyrosine kinases than c-Kit receptor. There was little influence of ABCB1 on TKI effects to the proliferation of VIMC1. These results will be helpful to understand the different sensitivity to TKIs in cMCT patients.

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Section: Discussionsupporting

confidence: 91%

Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses

Takeuchi

Fujino

Fukushima

et al. 2011

Vet Pharm & Therapeutics

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“…13 It is unclear whether these mutations play a causal or permissive role, where additional factors are necessary to develop ISM and/or ASM, and whether they may influence the response to different tyrosine kinase inhibitors, as suggested by in vitro studies with mast cell leukemia cell lines. 30 …”

Section: Discussionmentioning

confidence: 99%

Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease

Fernandes¹,

Teixeira

Freitas

et al. 2014

An. Bras. Dermatol.

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BACKGROUNDMastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs. OBJECTIVESTo present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease. METHODSThe cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated. RESULTSThe age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy. CONCLUSIONSCutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease.

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“…There is increasing evidence that different molecules have a specific effectiveness profile . The peculiarities depend on the type of substrate with TK activity as well as on the mutational status.…”

Section: Discussionmentioning

confidence: 99%

The use of COLD‐PCR, DHPLC and GeneScanning for the highly sensitive detection of c‐KIT somatic mutations in canine mast cell tumours

Gentilini

Mantovani

Turba³

2013

Vet Comparative Oncology

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The conventional polymerase chain reaction (PCR)/sequencing methods may be poorly suited for the detection of somatic mutations in canine mast cell tumour (MCT) samples owing to limited sensitivity. This study was aimed at establishing novel and more sensitive methods, assessing their limit of detection and comparing their sensitivity with conventional methods.Two different 'driver' somatic mutations of c-KIT, together with the wild-type counterparts, were cloned in plasmids to prepare standard samples with known concentrations of mutated alleles in a background of wild-type alleles; the plasmids standards were assayed using either conventional or novel, highly sensitive technique. Conventional PCR/sequencing showed a sensitivity of 50-20%. Conversely, all the novel methods obtained higher sensitivities allowed reaching as low as 2.5-1.2% of the mutated DNA.The study demonstrates that early conventional methods could likely have underestimated the prevalence of KIT mutations of MCTs, therefore affecting the assessment of their relevance in prognosis and tyrosine kinase inhibitor (TKI) treatment effectiveness.

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KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406)

Cited by 11 publications

References 53 publications

Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses

Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses

Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease

The use of COLD‐PCR, DHPLC and GeneScanning for the highly sensitive detection of c‐KIT somatic mutations in canine mast cell tumours

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