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Prognostic significance of ASXL1 mutation types and allele burden in myelofibrosis

Leukemia volume 32, pages 837–839 (2018)Cite this article

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The prognostic contribution of exon 12 additional sex comb-like 1 (ASXL1) mutations in primary myelofibrosis (PMF) is now well established1, 2; mutational frequency in newly diagnosed cases was reported at 22% and prognostic effect was shown to be independent of both the international prognostic scoring system (IPSS)3 and the dynamic IPSS (DIPSS)-plus;4 as well as driver mutational status (that is, presence or absence of CALR type 1/like mutation) and other high molecular risk mutations, including SRSF2 and EZH2.2 Phenotypically, ASXL1-mutated patients with PMF were older and displayed higher prevalence of leukocytosis.1 The adverse prognostic impact of ASXL1 mutations has also been demonstrated in other myeloid malignancies, including acute myeloid leukemia,5 myelodysplastic syndromes,6 chronic myelomonocytic leukemia,7 CSF3R-mutated chronic neutrophilic leukemia8 and aggressive forms of systemic mastocytosis.9 In myelodysplastic syndrome10 and chronic myelomonocytic leukemia,7 the prognostic effect of ASXL1 mutations has been attributed to frameshift or nonsense, as opposed to missense, mutations. In the current study, we examined the mutation type-specific prognostic impact of ASXL1 mutations in PMF, and also considered the possibility of further modification from mutant allele burden.

ASXL1 mutational status was available in 480 patients with PMF (median age 63 years, range 22–89, males 64%); median (range) values included hemoglobin level 10.3 g/dl (5.8–16.1), leukocyte count 8.9 × 10(9)/l (1–219) and platelet count 224 × 10(9)/l (11–2466). Driver mutational status was JAK2 in 259 (54%) patients, type 1/like CALR in 108 (23%), type 2/like CALR in 21 (4%), MPL in 31 (7%) and triple-negative in 61 (12%). DIPSS-plus risk distribution was 32% high, 37% intermediate-2, 18% intermediate-1 and 13% low. Information on karyotype was available in 472 patients, including 186 (39%) with abnormal karyotype and 45 (10%) with unfavorable karyotype. Median follow-up was 4.6 years (range 0.04–31) and during this period 338 (70%) deaths and 56 (12%) leukemic transformations were recorded.

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Authors and Affiliations

  1. Division of Hematology, Departments of Internal and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    A Tefferi, T L Lasho, C Finke, N Gangat & A Pardanani

  2. Division of Hematopathology, Departments of Internal and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    C A Hanson

  3. Division of Cytogenetics, Departments of Internal and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

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  1. A Tefferi
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  2. T L Lasho
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Correspondence to A Tefferi.

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Tefferi, A., Lasho, T., Finke, C. et al. Prognostic significance of ASXL1 mutation types and allele burden in myelofibrosis. Leukemia 32, 837–839 (2018). https://doi.org/10.1038/leu.2017.318

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