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Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high risk group of patients with KIT D816V+ advanced systemic mastocytosis

Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high risk group of patients with KIT D816V+ advanced systemic mastocytosis
Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high risk group of patients with KIT D816V+ advanced systemic mastocytosis
Most patients with KIT D816V+ advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V+ advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03) but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V+ SM. Based on these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.
0887-6924
136-143
Jawhar, M.
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Schwaab, J.
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Schnittger, S.
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Meggendorfer, M.
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Pfirrmann, M.
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Sotlar, K.
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Horny, H.-P.
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Metzgeroth, G.
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Kluger, S.
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Naumann, N.
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Haferlach, C.
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Haferlach, T.
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Valent, P.
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Hofmann, W.-K.
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Fabarius, A.
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Cross, N.C.P.
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Reiter, A.
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Jawhar, M.
f7cf628f-0346-439a-92c4-b9f4c635177e
Schwaab, J.
f4f67962-3582-4070-932d-19c71a1b4863
Schnittger, S.
ce0be363-7bac-461c-b9ab-2411906ce896
Meggendorfer, M.
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Pfirrmann, M.
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Sotlar, K.
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Horny, H.-P.
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Metzgeroth, G.
ce361b67-c4da-471c-95aa-acb1dd0d1b04
Kluger, S.
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Naumann, N.
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Haferlach, C.
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Haferlach, T.
f47018a2-5002-4a59-b57d-08f670382beb
Valent, P.
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Hofmann, W.-K.
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Fabarius, A.
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Cross, N.C.P.
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Reiter, A.
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Jawhar, M., Schwaab, J., Schnittger, S., Meggendorfer, M., Pfirrmann, M., Sotlar, K., Horny, H.-P., Metzgeroth, G., Kluger, S., Naumann, N., Haferlach, C., Haferlach, T., Valent, P., Hofmann, W.-K., Fabarius, A., Cross, N.C.P. and Reiter, A. (2016) Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high risk group of patients with KIT D816V+ advanced systemic mastocytosis. Leukemia, 30 (1), 136-143. (doi:10.1038/leu.2015.284).

Record type: Article

Abstract

Most patients with KIT D816V+ advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V+ advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03) but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V+ SM. Based on these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.

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Accepted/In Press date: 29 September 2015
e-pub ahead of print date: 10 November 2015
Published date: January 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 383043
URI: http://eprints.soton.ac.uk/id/eprint/383043
ISSN: 0887-6924
PURE UUID: f8d1d276-37d2-44f8-966d-fd24afc7db9b
ORCID for N.C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 27 Oct 2015 14:08
Last modified: 17 Dec 2019 01:51

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Contributors

Author: M. Jawhar
Author: J. Schwaab
Author: S. Schnittger
Author: M. Meggendorfer
Author: M. Pfirrmann
Author: K. Sotlar
Author: H.-P. Horny
Author: G. Metzgeroth
Author: S. Kluger
Author: N. Naumann
Author: C. Haferlach
Author: T. Haferlach
Author: P. Valent
Author: W.-K. Hofmann
Author: A. Fabarius
Author: N.C.P. Cross ORCID iD
Author: A. Reiter

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