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PLoS One. 2014 Jan 21;9(1):e85362. doi: 10.1371/journal.pone.0085362. eCollection 2014.

ASXL1 but not TET2 mutations adversely impact overall survival of patients suffering systemic mastocytosis with associated clonal hematologic non-mast-cell diseases.

Author information

  • 1Service d'Hématologie, Centre Hospitalier Universitaire, Hôpital Sud; Amiens, France ; Centre de Référence des Mastocytoses, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France ; CNRS UMR 8147 and Institut Imagine, AP-HP, Hôpital Necker-Enfants Malades, Paris, France.
  • 2Service d'Hématologie, Centre Hospitalier Universitaire, Hôpital Sud; Amiens, France.
  • 3Centre de Référence des Mastocytoses, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France ; Service d'Hématologie Adulte, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
  • 4Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis); Institut Paoli-Calmettes,Marseille; Aix-Marseille Univ; CNRS, UMR7258, Marseille, France.
  • 5Service d'Anatomo-pathologie, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
  • 6Service d'Hématologie, Centre Hospitalier Universitaire, Reims, France.
  • 7Service de médecine interne, Groupe Hospitalier Sud. Hospices Civils, Lyon, France.
  • 8Service d'Hématologie et thérapie cellulaire, CIC INSERMU202, Centre Hospitalier Universitaire, Tours, France.
  • 9Département de Dermatologie, Centre Hospitalier Universitaire, Toulouse, France.
  • 10Service d'Hématologie, Centre Hospitalier Universitaire, Caen, France.
  • 11Département de bio-statistiques et de Recherche clinique, Centre Hospitalier Universitaire, Amiens, France.
  • 12Service d'Hématologie, Centre Hospitalier, St Quentin, France.
  • 13Service de Médecine Interne, Hôpital Tenon, Assistance Publique-Hôpitaux, Université Pierre et Marie Curie, Paris, France.
  • 14Laboratoire d'hématologie Biologique et UMR CNRS 8147, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et Assistance Publique-Hôpitaux de Paris (AP-HP) Necker-Enfants Malades, Paris, France.
  • 15Service d'Hématologie, Centre Hospitalier Universitaire, Angers, France.
  • 16Service de Médecine Interne, CHRU, Lille, France.
  • 17CNRS UMR 8113, Laboratoire de Biologie et Pharmacologie Appliquée, Ecole Normale Supérieure, Cachan, France ; Laboratoire Central d'Hématologie, Groupe Hospitalier Pitié-Salpetrière, Paris, France.
  • 18Service de Médecine Interne et de Maladie Infectieuses, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
  • 19Centre de Référence des Mastocytoses, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France ; CNRS UMR 8147 and Institut Imagine, AP-HP, Hôpital Necker-Enfants Malades, Paris, France ; Service d'Hématologie Adulte, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.

Abstract

Systemic mastocytosis with associated hematologic clonal non-mast cell disease (SM-AHNMD) is a rare and heterogeneous subtype of SM and few studies on this specific entity have been reported. Sixty two patients with Systemic mastocytosis with associated hematologic clonal non-mast cell disease (SM-AHNMD) were presented. Myeloid AHNMD was the most frequent (82%) cases. This subset of patients were older, had more cutaneous lesions, splenomegaly, liver enlargement, ascites; lower bone mineral density and hemoglobin levels and higher tryptase level than lymphoid AHNMD. Defects in KIT, TET2, ASXL1 and CBL were positive in 87%, 27%, 14%, and 11% of cases respectively. The overall survival of patients with SM-AHNMD was 85.2 months. Within the myeloid group, SM-MPN fared better than SM-MDS or SM-AML (p = 0.044,). In univariate analysis, the presence of C-findings, the AHNMD subtypes (SM-MDS/CMML/AML versus SM-MPN/hypereosinophilia) (p = 0.044), Neutropenia (p = 0.015), high monocyte level (p = 0.015) and the presence of ASXL1 mutation had detrimental effects on OS (p = 0.007). In multivariate analysis and penalized Cox model, only the presence of ASXL1 mutation remained an independent prognostic factor that negatively affected OS (p = 0.035). SM-AHNMD is heterogeneous with variable prognosis according to the type of the AHNMD. ASXL1 is mutated in a subset of myeloid AHNMD and adversely impact on OS.

PMID:
24465546
[PubMed - indexed for MEDLINE]
PMCID:
PMC3897447
Free PMC Article
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