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

Jawhar, Mohamad; Schwaab, Juliana; Schnittger, Susanne; Meggendorfer, Manja; Pfirrmann, Markus; Sotlar, Karl; Horny, Hans‐Peter; Metzgeroth, Georgia; Kluger, Sebastian; Naumann, Nicole; Haferlach, Claudia; Haferlach, Torsten; Valent, Peter; Hofmann, Wolf‐Karsten; Fabarius, Alice; Cross, Nicholas C. P.; Reiter, Andreas

doi:10.1038/leu.2015.284

Cited by 188 publications

(213 citation statements)

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“…11 We therefore included mutation profiles in our analyses and delineated Clinical, laboratory and magnet resonance imaging (MRI) derived # volumetric analysis and findings of 108 patients with systemic mastocytosis, stratified by spleen volume < 450 mL (no splenomegaly), ≥ 450 mL and < 1200 mL (mild splenomegaly) or ≥ 1200 mL (marked splenomegaly).…”

Section: Discussionmentioning

confidence: 99%

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Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

et al. 2016

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Section: Discussionmentioning

confidence: 99%

“…6,[8][9][10] Furthermore, the presence and number of molecular aberrations, e.g. in SRSF2, ASXL, or RUNX1 (S/A/R gene panel), have a strong adverse impact on disease phenotype and OS in patients with advSM.. 9,11 One of several WHO criteria to classify SM includes enlargement of visceral organs, e.g. spleen, liver, or lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

et al. 2016

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“…64,72 In a recent study, Jawhar et al have analyzed the impact of several additional defects on 70 multi-mutated KIT D816V+ patients with an AHN. 77 In this study, 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). 77 In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS.…”

Section: Progress In Somatic Mutations Other Than Kit In Smmentioning

confidence: 99%

“…77 In this study, 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). 77 In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, the authors 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).…”

Section: Progress In Somatic Mutations Other Than Kit In Smmentioning

confidence: 99%

“…Furthermore, the authors 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). 77 It appears that, based on these findings, the inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM. This might be particularly important for patients with SM-AHN given that most of these studies were done in patients with SM-AHN.…”

Section: Progress In Somatic Mutations Other Than Kit In Smmentioning

confidence: 99%

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Advanced systemic mastocytosis: from molecular and genetic progress to clinical practice

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International audienceSystemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all systemic mastocytosis patients. While most systemic mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called “advanced systemic mastocytosis”, which include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia. Whereas patients with indolent systemic mastocytosis have a near normal life expectancy, patients with advanced systemic mastocytosis have a reduced life expectancy. Although cladribine and interferon-alpha are of benefit in a group of patients with advanced systemic mastocytosis, no curative therapy is available for these patients except possible allogeneic hematopoietic stem cell transplantation. Recent studies have also revealed additional somatic defects (apart from mutations in KIT) in a majority of patients with advanced systemic mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS mutations, which may adversely impact prognosis and survival in particular systemic mastocytosis with an associated hematological neoplasm. In addition, several additional signaling molecules involved in the abnormal proliferation of mast cells in systemic mastocytosis have been identified. These advances have led to a better understanding of the biology of advanced systemic mastocytosis and to the development of new targeted treatment concepts. Herein, we review the biology and pathogenesis of advanced systemic mastocytosis, with a special focus on novel molecular findings as well as current and evolving therapeutic options

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Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms

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2019

Adv Cell Gene Ther

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In recent years, a large body of knowledge regarding the molecular genetics of myeloid malignancies has emerged and molecular findings have become increasingly important not only for diagnosis but also to establish prognosis and treatment of patients with myeloid malignancies. Clinical and pathological findings have been refined in relation to their diagnostic/prognostic value. The integration of all these different parameters represents the backbone of the 2016 revised 4th Edition of the WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. The current review aims to highlight the main changes between the 2008 WHO Classification and the most recent 2016 revised 4th edition, with regard to the classification of myeloid malignancies. K E Y W O R D S Acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative neoplasms, WHO classification 2 of 9 | SANGIORGIO ANd ORAZI 2.2 | BCR-ABL1 negative myeloproliferative neoplasms | Polycythemia veraMajor changes in the clinical criteria for the diagnosis of polycythemia vera (PV) have been adopted in the revised classification. Hemoglobin (Hb) >18.5 g/dL for men and > 16.5 g/dL for women were the thresholds used to diagnose PV in the 2008 classification. Applying these criteria, many cases of early phase PV were left unrecognized, for example, patients with a red cell mass > 25% of the mean predicted value (thus indicative of increased red cell volume), but with Hb level falling below the stated thresholds. For such cases, the definition of "masked PV" has been introduced. 7,8 Similarly, application of the 2008 criteria can lead to misdiagnose as essential thrombocythemia (ET) cases of early PV presenting with thrombocytosis. 9,10 To address these issues, the revised classification has established Hb > 16.5 for men and > 16.0 for women as the new thresholds for the diagnosis of PV. The newer TA B L E 1 Summary of the major diagnostic changes introduced by the 2016 WHO classification, revised 4th edition

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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

Cited by 188 publications

References 36 publications

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

Advanced systemic mastocytosis: from molecular and genetic progress to clinical practice

Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms

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