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Mutations and prognosis in primary myelofibrosis

Mutations and prognosis in primary myelofibrosis
Mutations and prognosis in primary myelofibrosis
Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; P<0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P=0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations. Mutational profiling for ASXL1, EZH2, SRSF2 and IDH identifies PMF patients who are at risk for premature death or leukemic transformation
0887-6924
1861-1869
Vannucchi, A.M.
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Lasho, T.L.
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Guglielmelli, P.
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Biamonte, F.
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Pardanani, A.
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Pereira, A.
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Finke, C.
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Score, J.
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Gangat, N.
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Mannarelli, C.
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Ketterling, R.P.
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Rotunno, G.
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Knudson, R.A.
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Susini, M.C.
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Laborde, R.R.
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Spolverini, A.
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Pancrazzi, A.
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Pieri, L.
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Manfredini, R.
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Tagliafico, E.
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Zini, R.
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Jones, A.
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Zoi, K.
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Reiter, A.
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Duncombe, A
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Pietra, D.
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Rumi, E.
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Cervantes, F.
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Barosi, G.
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Cazzola, M.
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Cross, N.C.P.
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Tefferi, A.
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Vannucchi, A.M.
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Lasho, T.L.
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Guglielmelli, P.
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Biamonte, F.
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Pardanani, A.
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Pereira, A.
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Finke, C.
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Score, J.
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Gangat, N.
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Mannarelli, C.
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Ketterling, R.P.
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Rotunno, G.
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Knudson, R.A.
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Susini, M.C.
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Laborde, R.R.
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Spolverini, A.
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Pancrazzi, A.
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Pieri, L.
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Manfredini, R.
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Tagliafico, E.
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Zini, R.
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Jones, A.
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Zoi, K.
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Reiter, A.
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Duncombe, A
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Pietra, D.
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Rumi, E.
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Cervantes, F.
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Barosi, G.
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Cazzola, M.
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Cross, N.C.P.
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Tefferi, A.
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Vannucchi, A.M., Lasho, T.L., Guglielmelli, P., Biamonte, F., Pardanani, A., Pereira, A., Finke, C., Score, J., Gangat, N., Mannarelli, C., Ketterling, R.P., Rotunno, G., Knudson, R.A., Susini, M.C., Laborde, R.R., Spolverini, A., Pancrazzi, A., Pieri, L., Manfredini, R., Tagliafico, E., Zini, R., Jones, A., Zoi, K., Reiter, A., Duncombe, A, Pietra, D., Rumi, E., Cervantes, F., Barosi, G., Cazzola, M., Cross, N.C.P. and Tefferi, A. (2013) Mutations and prognosis in primary myelofibrosis. Leukemia, 27 (9), 1861-1869. (doi:10.1038/leu.2013.119). (PMID:23619563)

Record type: Article

Abstract

Patient outcome in primary myelofibrosis (PMF) is significantly influenced by karyotype. We studied 879 PMF patients to determine the individual and combinatorial prognostic relevance of somatic mutations. Analysis was performed in 483 European patients and the seminal observations were validated in 396 Mayo Clinic patients. Samples from the European cohort, collected at time of diagnosis, were analyzed for mutations in ASXL1, SRSF2, EZH2, TET2, DNMT3A, CBL, IDH1, IDH2, MPL and JAK2. Of these, ASXL1, SRSF2 and EZH2 mutations inter-independently predicted shortened survival. However, only ASXL1 mutations (HR: 2.02; P<0.001) remained significant in the context of the International Prognostic Scoring System (IPSS). These observations were validated in the Mayo Clinic cohort where mutation and survival analyses were performed from time of referral. ASXL1, SRSF2 and EZH2 mutations were independently associated with poor survival, but only ASXL1 mutations held their prognostic relevance (HR: 1.4; P=0.04) independent of the Dynamic IPSS (DIPSS)-plus model, which incorporates cytogenetic risk. In the European cohort, leukemia-free survival was negatively affected by IDH1/2, SRSF2 and ASXL1 mutations and in the Mayo cohort by IDH1 and SRSF2 mutations. Mutational profiling for ASXL1, EZH2, SRSF2 and IDH identifies PMF patients who are at risk for premature death or leukemic transformation

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More information

Published date: September 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 359220
URI: http://eprints.soton.ac.uk/id/eprint/359220
ISSN: 0887-6924
PURE UUID: 94927309-1fee-487f-9313-7f2c31ee9f54
ORCID for N.C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 24 Oct 2013 10:52
Last modified: 28 Apr 2022 01:49

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Contributors

Author: A.M. Vannucchi
Author: T.L. Lasho
Author: P. Guglielmelli
Author: F. Biamonte
Author: A. Pardanani
Author: A. Pereira
Author: C. Finke
Author: J. Score
Author: N. Gangat
Author: C. Mannarelli
Author: R.P. Ketterling
Author: G. Rotunno
Author: R.A. Knudson
Author: M.C. Susini
Author: R.R. Laborde
Author: A. Spolverini
Author: A. Pancrazzi
Author: L. Pieri
Author: R. Manfredini
Author: E. Tagliafico
Author: R. Zini
Author: A. Jones
Author: K. Zoi
Author: A. Reiter
Author: A Duncombe
Author: D. Pietra
Author: E. Rumi
Author: F. Cervantes
Author: G. Barosi
Author: M. Cazzola
Author: N.C.P. Cross ORCID iD
Author: A. Tefferi

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