title: High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.
abstract: Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome.
  
  
  CONCLUSIONS
  Mutations of key transcription factor in myeloid malignancies.
authors.affiliation: Department of Hematology, Centre Hospitalier Universitaire Toulouse Purpan, Toulouse, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Pasquet
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tavitian
authors.forename: Naïs
authors.initials: N
authors.lastname: Prade
authors.forename: Blandine
authors.initials: B
authors.lastname: Beaupain
authors.forename: Olivier
authors.initials: O
authors.lastname: Larochelle
authors.forename: Arnaud
authors.initials: A
authors.lastname: Petit
authors.forename: Pierre
authors.initials: P
authors.lastname: Rohrlich
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.forename: Hélène A
authors.initials: HA
authors.lastname: Poirel
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Marie
authors.initials: M
authors.lastname: Ouachée-Chardin
authors.forename: Véronique
authors.initials: V
authors.lastname: Mansat-De Mas
authors.forename: Jill
authors.initials: J
authors.lastname: Corre
authors.forename: Christian
authors.initials: C
authors.lastname: Récher
authors.forename: Geneviève
authors.initials: G
authors.lastname: Plat
authors.forename: Françoise
authors.initials: F
authors.lastname: Bachelerie
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D050989:GATA2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D056426:Genetic Loci; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D020125:Mutation, Missense; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009503:Neutropenia / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D012042:Registries
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human