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

The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis
The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis
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.
81-88
Erben, Philipp
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Schwaab, Juliana
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Metzgeroth, Georgia
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Horny, Hans-Peter
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Jawhar, Mohamad
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Sotlar, Karl
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Fabarius, Alice
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Teichmann, Martina
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Schneider, Sven
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Ernst, Thomas
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Müller, Martin C.
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Giehl, Michelle
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Marx, Alexander
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Hartmann, Karin
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Hochhaus, Andreas
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Hofmann, Wolf-Karsten
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Cross, Nicholas C.P.
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Reiter, Andreas
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Erben, Philipp
defa0bda-e318-499b-9f62-36288a8407ae
Schwaab, Juliana
d63ed545-a6fc-4815-ab86-f901e55c2a2f
Metzgeroth, Georgia
611ec46d-9a11-4e24-ae0f-5ac19dfd0237
Horny, Hans-Peter
95077a3b-b869-49ba-a227-f88b2c0bad80
Jawhar, Mohamad
a608a215-173b-47bd-89eb-a8de2fe595aa
Sotlar, Karl
e3e96797-3fab-4c37-8728-7c77bb3ba389
Fabarius, Alice
5c31b1e0-c6da-49b8-843a-5b0ca736e5a2
Teichmann, Martina
442c1152-a8d8-470f-a056-4be94bb4efb8
Schneider, Sven
ac4f9067-8e44-4ef0-bdc3-0a2d4b4684b8
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Müller, Martin C.
ea37982c-00bb-44b5-bc73-f4b5bd0825e9
Giehl, Michelle
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Marx, Alexander
d2253ef6-a356-4bc1-87e4-1ea0f7b8f0aa
Hartmann, Karin
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Hochhaus, Andreas
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Hofmann, Wolf-Karsten
ab66838b-bf8c-4352-a0f0-3c8aafed2570
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede

Erben, Philipp, Schwaab, Juliana, Metzgeroth, Georgia, Horny, Hans-Peter, Jawhar, Mohamad, Sotlar, Karl, Fabarius, Alice, Teichmann, Martina, Schneider, Sven, Ernst, Thomas, Müller, Martin C., Giehl, Michelle, Marx, Alexander, Hartmann, Karin, Hochhaus, Andreas, 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. Annals of Hematology, 93 (1), 81-88. (doi:10.1007/s00277-013-1964-1). (PMID:24281161)

Record type: Article

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.

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More information

Accepted/In Press date: 27 November 2013
Published date: 2014
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 360223
URI: http://eprints.soton.ac.uk/id/eprint/360223
PURE UUID: 8ef45237-76c6-4f78-9be7-5e97128e4743
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 29 Nov 2013 14:19
Last modified: 15 Mar 2024 03:11

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Contributors

Author: Philipp Erben
Author: Juliana Schwaab
Author: Georgia Metzgeroth
Author: Hans-Peter Horny
Author: Mohamad Jawhar
Author: Karl Sotlar
Author: Alice Fabarius
Author: Martina Teichmann
Author: Sven Schneider
Author: Thomas Ernst
Author: Martin C. Müller
Author: Michelle Giehl
Author: Alexander Marx
Author: Karin Hartmann
Author: Andreas Hochhaus
Author: Wolf-Karsten Hofmann
Author: Andreas Reiter

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