Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome

Summary Background Children with Down's syndrome have a greatly increased risk of acute megakaryoblastic and acute lymphoblastic leukaemias. Acute megakaryoblastic leukaemia in Down's syndrome is characterised by a somatic mutation in GATA1 . Constitutive activation of the JAK/STAT (Janus...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Lancet (British edition) 2008-10, Vol.372 (9648), p.1484-1492
Hauptverfasser: Bercovich, Dani, PhD, Ganmore, Ithamar, BMedSc, Scott, Linda M, PhD, Wainreb, Gilad, MSc, Birger, Yehudit, PhD, Elimelech, Arava, MSc, Shochat, Chen, MSc, Cazzaniga, Giovanni, PhD, Biondi, Andrea, MD, Basso, Giuseppe, Prof, Cario, Gunnar, MD, Schrappe, Martin, Prof, Stanulla, Martin, Prof, Strehl, Sabine, PhD, Haas, Oskar A, Prof, Mann, Georg, MD, Binder, Vera, MD, Borkhardt, Arndt, Prof, Kempski, Helena, PhD, Trka, Jan, Prof, Bielorei, Bella, MD, Avigad, Smadar, PhD, Stark, Batia, Prof, Smith, Owen, Prof, Dastugue, Nicole, PhD, Bourquin, Jean-Pierre, MD, Tal, Nir Ben, Prof, Green, Anthony R, Prof, Izraeli, Shai, Prof
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Summary Background Children with Down's syndrome have a greatly increased risk of acute megakaryoblastic and acute lymphoblastic leukaemias. Acute megakaryoblastic leukaemia in Down's syndrome is characterised by a somatic mutation in GATA1 . Constitutive activation of the JAK/STAT (Janus kinase and signal transducer and activator of transcription) pathway occurs in several haematopoietic malignant diseases. We tested the hypothesis that mutations in JAK2 might be a common molecular event in acute lymphoblastic leukaemia associated with Down's syndrome. Methods JAK2 DNA mutational analysis was done on diagnostic bone marrow samples obtained from 88 patients with Down's syndrome-associated acute lymphoblastic leukaemia; and 216 patients with sporadic acute lymphoblastic leukaemia, Down's syndrome-associated acute megakaryoblastic leukaemia, and essential thrombocythaemia. Functional consequences of identified mutations were studied in mouse haematopoietic progenitor cells. Findings Somatically acquired JAK2 mutations were identified in 16 (18%) patients with Down's syndrome-associated acute lymphoblastic leukaemia. The only patient with non-Down's syndrome-associated leukaemia but with a JAK2 mutation had an isochromosome 21q. Children with a JAK2 mutation were younger (mean [SE] age 4·5 years [0·86] vs 8·6 years [0·59], p
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(08)61341-0