Mutations and prognosis in primary myelofibrosis

A. M. Vannucchi, T. L. Lasho, P. Guglielmelli, F. Biamonte, Animesh D Pardanani, A. Pereira, C. Finke, J. Score, N. Gangat, C. Mannarelli, R. P. Ketterling, G. Rotunno, R. A. Knudson, M. C. Susini, R. R. Laborde, A. Spolverini, A. Pancrazzi, L. Pieri, R. Manfredini, E. Tagliafico & 12 others R. Zini, A. Jones, K. Zoi, A. Reiter, A. Duncombe, D. Pietra, E. Rumi, F. Cervantes, G. Barosi, M. Cazzola, N. C P Cross, Ayalew Tefferi

Research output: Contribution to journalArticle

364 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1861-1869
Number of pages9
JournalLeukemia
Volume27
Issue number9
DOIs
StatePublished - Sep 2013

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Primary Myelofibrosis
Mutation
Survival
Premature Mortality
Survival Analysis
Karyotype
Cytogenetics
Leukemia
Cohort Studies
Referral and Consultation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Vannucchi, A. M., Lasho, T. L., Guglielmelli, P., Biamonte, F., Pardanani, A. D., Pereira, A., ... Tefferi, A. (2013). Mutations and prognosis in primary myelofibrosis. Leukemia, 27(9), 1861-1869. https://doi.org/10.1038/leu.2013.119

Mutations and prognosis in primary myelofibrosis. / Vannucchi, A. M.; Lasho, T. L.; Guglielmelli, P.; Biamonte, F.; Pardanani, Animesh D; 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; Tefferi, Ayalew.

In: Leukemia, Vol. 27, No. 9, 09.2013, p. 1861-1869.

Research output: Contribution to journalArticle

Vannucchi, AM, Lasho, TL, Guglielmelli, P, Biamonte, F, Pardanani, AD, Pereira, A, Finke, C, Score, J, Gangat, N, Mannarelli, C, Ketterling, RP, Rotunno, G, Knudson, RA, Susini, MC, Laborde, RR, 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, NCP & Tefferi, A 2013, 'Mutations and prognosis in primary myelofibrosis', Leukemia, vol. 27, no. 9, pp. 1861-1869. https://doi.org/10.1038/leu.2013.119
Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani AD, Pereira A et al. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013 Sep;27(9):1861-1869. https://doi.org/10.1038/leu.2013.119
Vannucchi, A. M. ; Lasho, T. L. ; Guglielmelli, P. ; Biamonte, F. ; Pardanani, Animesh D ; 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 ; Tefferi, Ayalew. / Mutations and prognosis in primary myelofibrosis. In: Leukemia. 2013 ; Vol. 27, No. 9. pp. 1861-1869.
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AU - Pardanani, Animesh D

AU - Pereira, A.

AU - Finke, C.

AU - Score, J.

AU - Gangat, N.

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AU - Reiter, A.

AU - Duncombe, A.

AU - Pietra, D.

AU - Rumi, E.

AU - Cervantes, F.

AU - Barosi, G.

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AU - Cross, N. C P

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