ASXL1 but not TET2 mutations adversely impact overall survival of patients suffering systemic mastocytosis with associated clonal hematologic non-mast-cell diseases.
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.
Service 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.
Gandhi
G
Damaj
Service d'Hématologie, Centre Hospitalier Universitaire, Hôpital Sud; Amiens, France.
Magalie
M
Joris
Centre 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.
Olivia
O
Chandesris
Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis); Institut Paoli-Calmettes,Marseille; Aix-Marseille Univ; CNRS, UMR7258, Marseille, France.
Katia
K
Hanssens
Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis); Institut Paoli-Calmettes,Marseille; Aix-Marseille Univ; CNRS, UMR7258, Marseille, France.
Erinn
E
Soucie
Service d'Anatomo-pathologie, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
Danielle
D
Canioni
Service d'Hématologie, Centre Hospitalier Universitaire, Reims, France.
Brigitte
B
Kolb
Service de médecine interne, Groupe Hospitalier Sud. Hospices Civils, Lyon, France.
Isabelle
I
Durieu
Service d'Hématologie et thérapie cellulaire, CIC INSERMU202, Centre Hospitalier Universitaire, Tours, France.
Emanuel
E
Gyan
Département de Dermatologie, Centre Hospitalier Universitaire, Toulouse, France.
Cristina
C
Livideanu
Service d'Hématologie, Centre Hospitalier Universitaire, Caen, France.
Stephane
S
Chèze
Département de bio-statistiques et de Recherche clinique, Centre Hospitalier Universitaire, Amiens, France.
Momar
M
Diouf
Service d'Hématologie, Centre Hospitalier, St Quentin, France.
Reda
R
Garidi
Service de Médecine Interne, Hôpital Tenon, Assistance Publique-Hôpitaux, Université Pierre et Marie Curie, Paris, France.
Sophie
S
Georgin-Lavialle
Laboratoire 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.
Vahid
V
Asnafi
Laboratoire 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.
Ludovic
L
Lhermitte
Service d'Hématologie, Centre Hospitalier Universitaire, Angers, France.
Christian
C
Lavigne
Service de Médecine Interne, CHRU, Lille, France.
David
D
Launay
CNRS UMR 8113, Laboratoire de Biologie et Pharmacologie Appliquée, Ecole Normale Supérieure, Cachan, France ; Laboratoire Central d'Hématologie, Groupe Hospitalier Pitié-Salpetrière, Paris, France.
Michel
M
Arock
Service de Médecine Interne et de Maladie Infectieuses, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
Olivier
O
Lortholary
Inserm, U1068, CRCM, (Signaling, Hematopoiesis and Mechanism of Oncogenesis); Institut Paoli-Calmettes,Marseille; Aix-Marseille Univ; CNRS, UMR7258, Marseille, France.
Patrice
P
Dubreuil
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 ; Service d'Hématologie Adulte, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
Olivier
O
Hermine
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D034721:Mastocytosis, Systemic / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009154:Mutation; D009503:Neutropenia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D016019:Survival Analysis
C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; D050721:Proto-Oncogene Proteins c-cbl; D019009:Proto-Oncogene Proteins c-kit; C067419:CBL protein, human