NDLI: Adverse Prognostic Impact of the KIT D816V Transcriptional Activity in Advanced Systemic Mastocytosis

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Adverse Prognostic Impact of the KIT D816V Transcriptional Activity in Advanced Systemic Mastocytosis

Content Provider	MDPI
Author	Johannes, Lübke Naumann, Nicole Baumann, Sofie Schwaab, Juliana Hoffmann, Oliver Kreil, Sebastian Dangelo, Vito Reiter, Lukas Bugert, Peter Kristensen, Thomas Sotlar, Karl Haselmann, Verena Schneider, Sven Metzgeroth, Georgia Weiss, Christel Popp, Henning Fabarius, Alice Hofmann, Wolf-Karsten Cross, Nicholas Reiter, Andreas Jawhar, Mohamad
Copyright Year	2021
Description	In systemic mastocytosis (SM), qualitative and serial quantitative assessment of the KIT D816V mutation is of diagnostic and prognostic relevance. We investigated peripheral blood and bone marrow samples of 161 patients (indolent SM (ISM), n = 40; advanced SM, AdvSM, n = 121) at referral and during follow-up for the KIT D816V variant allele frequency (VAF) at the DNA-level and the KIT D816V expressed allele burden (EAB) at the RNA-level. A round robin test with four participating laboratories revealed an excellent correlation (r > 0.99, R2 > 0.98) between three different DNA-assays. VAF and EAB strongly correlated in ISM (r = 0.91, coefficient of determination, R2 = 0.84) but only to a lesser extent in AdvSM (r = 0.71; R2 = 0.5). However, as compared to an EAB/VAF ratio ≤2 (cohort A, 77/121 patients, 64%) receiver operating characteristic (ROC) analysis identified an EAB/VAF ratio of >2 (cohort B, 44/121 patients, 36%) as predictive for an advanced phenotype and a significantly inferior median survival (3.3 vs. 11.7 years; p = 0.005). In terms of overall survival, Cox-regression analysis was only significant for the EAB/VAF ratio >2 (p = 0.006) but not for VAF or EAB individually. This study demonstrates for the first time that the transcriptional activity of KIT D816V may play an important role in the pathophysiology of SM.
Starting Page	2562
e-ISSN	14220067
DOI	10.3390/ijms22052562
Journal	International Journal of Molecular Sciences
Issue Number	5
Volume Number	22
Language	English
Publisher	MDPI
Publisher Date	2021-03-04
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Endocrinology and Metabolism Advanced Sm Kit D816v Allele Burden Variant Allele Frequency Survival
Content Type	Text
Resource Type	Article

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