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The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis

Erben, Philipp and Schwaab, Juliana and Metzgeroth, Georgia and Horny, Hans-Peter and Jawhar, Mohamad and Sotlar, Karl and Fabarius, Alice and Teichmann, Martina and Schneider, Sven and Ernst, Thomas and Müller, Martin C. and Giehl, Michelle and Marx, Alexander and Hartmann, Karin and Hochhaus, Andreas and Hofmann, Wolf-Karsten and Cross, Nicholas C. P. and Reiter, Andreas. (2014) The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis. Annals of Hematology, 93 (1). pp. 81-88.

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Official URL: https://edoc.unibas.ch/70777/

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Abstract

The activating KIT D816V mutation plays a central role in the pathogenesis, diagnosis, and targeted treatment of systemic mastocytosis (SM). For improved and reliable identification of KIT D816V, we have developed an allele-specific quantitative real-time PCR (RQ-PCR) with an enhanced sensitivity of 0.01-0.1 %, which was superior to denaturing high-performance liquid chromatography (0.5-1 %) or conventional sequencing (10-20 %). Overall, KIT D816 mutations were identified in 146/147 (99 %) of patients (D816V, n = 142; D816H, n = 2; D816Y, n = 2) with SM, including indolent SM (ISM, n = 63, 43 %), smoldering SM (n = 8, 5 %), SM with associated hematological non-mast cell lineage disease (SM-AHNMD, n = 16, 11 %), and aggressive SM/mast cell leukemia ± AHNMD (ASM/MCL, n = 60, 41 %). If positive in BM, the KIT D816V mutation was found in PB of all patients with advanced SM (SM-AHNMD, ASM, and MCL) and in 46 % (23/50) of patients with ISM. There was a strong correlation between the KIT D816V expressed allele burden (KIT D816V EAB) with results obtained from DNA by genomic allele-specific PCR and also with disease activity (e.g., serum tryptase level), disease subtype (e.g., indolent vs. advanced SM) and survival. In terms of monitoring of residual disease, qualitative and quantitative assessment of KIT D816V and KIT D816V EAB was successfully used for sequential analysis after chemotherapy or allogeneic stem cell transplantation. We therefore conclude that RQ-PCR assays for KIT D816V are useful complimentary tools for diagnosis, disease monitoring, and evaluation of prognosis in patients with SM.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer Verlag
ISSN:0939-5555
e-ISSN:1432-0584
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Nov 2020 16:49
Deposited On:10 Nov 2020 16:49

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