Universität zu Köln

Erben, Philipp ORCID: 0000-0002-8279-7636, Schwaab, Juliana, Metzgeroth, Georgia, Horny, Hans-Peter, Jawhar, Mohamad, Sotlar, Karl, Fabarius, Alice, Teichmann, Martina, Schneider, Sven, Ernst, Thomas, Mueller, Martin C., Giehl, Michelle, Marx, Alexander, Hartmann, Karin ORCID: 0000-0002-4595-8226, Hochhaus, Andreas ORCID: 0000-0003-0626-0834, Hofmann, Wolf-Karsten, Cross, Nicholas C. P. and Reiter, Andreas (2014). The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis. Ann. Hematol., 93 (1). S. 81 - 89. NEW YORK: SPRINGER. ISSN 1432-0584

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Erben, Philipp UNSPECIFIED orcid.org/0000-0002-8279-7636 UNSPECIFIED Schwaab, Juliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Metzgeroth, Georgia UNSPECIFIED UNSPECIFIED UNSPECIFIED Horny, Hans-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Jawhar, Mohamad UNSPECIFIED UNSPECIFIED UNSPECIFIED Sotlar, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabarius, Alice UNSPECIFIED UNSPECIFIED UNSPECIFIED Teichmann, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Ernst, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Martin C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giehl, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Marx, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Karin UNSPECIFIED orcid.org/0000-0002-4595-8226 UNSPECIFIED Hochhaus, Andreas UNSPECIFIED orcid.org/0000-0003-0626-0834 UNSPECIFIED Hofmann, Wolf-Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Cross, Nicholas C. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiter, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-451718
DOI:	10.1007/s00277-013-1964-1
Journal or Publication Title:	Ann. Hematol.
Volume:	93
Number:	1
Page Range:	S. 81 - 89
Date:	2014
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0584
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WORLD-HEALTH-ORGANIZATION; POLYMERASE-CHAIN-REACTION; MAST-CELL LEUKEMIA; RESPONSE CRITERIA; RESIDUAL DISEASE; SM-AHNMD; MUTATION; CLASSIFICATION; MARROW; NEOPLASMS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45171