title: ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia.
abstract: Chronic myelomonocytic leukaemia (CMML) is a haematological disease currently classified in the category of myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) because of its dual clinical and biological presentation. The molecular biology of CMML is poorly characterized. We studied a series of 53 CMML samples including 31 cases of myeloproliferative form (MP-CMML) and 22 cases of myelodysplastic forms (MD-CMML) using array-comparative genomic hybridisation (aCGH) and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1. Mutations in ASXL1 and in the genes associated with proliferation (CBL, FLT3, PTPN11, NRAS) were mainly found in MP-CMML cases. Mutations of ASXL1 correlated with an evolution toward an acutely transformed state: all CMMLs that progressed to acute phase were mutated and none of the unmutated patients had evolved to acute leukaemia. The overall survival of ASXL1 mutated patients was lower than that of unmutated patients.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Institut Paoli-Calmettes, Université de la Méditerranée Aix-Marseille II, Marseille, France. gelsiv@marseille.fnclcc.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Gelsi-Boyer
authors.forename: Virginie
authors.initials: V
authors.lastname: Trouplin
authors.forename: Julien
authors.initials: J
authors.lastname: Roquain
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Nadine
authors.initials: N
authors.lastname: Carbuccia
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Anne
authors.initials: A
authors.lastname: Murati
authors.forename: Christine
authors.initials: C
authors.lastname: Arnoulet
authors.forename: Hacène
authors.initials: H
authors.lastname: Zerazhi
authors.forename: Hacène
authors.initials: H
authors.lastname: Fezoui
authors.forename: Zoulika
authors.initials: Z
authors.lastname: Tadrist
authors.forename: Meyer
authors.initials: M
authors.lastname: Nezri
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D052138:Genes, Neoplasm; D056726:Genetic Association Studies; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C473949:ASXL1 protein, human; D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000090243:Nucleophosmin