title: Prevalence and clinical correlates of JAK2 mutations in Down syndrome acute lymphoblastic leukaemia.
abstract: Recurrent, prognostically significant chromosomal abnormalities occur in approximately 75% of paediatric acute lymphoblastic leukaemia (ALL), but only infrequently in children with Down syndrome (DS) and ALL. Recently, novel somatic activating mutations in the gene Janus kinase 2 (JAK2) were reported in 18% of DS ALL. Here we report identification and clinical correlates of JAK2 mutations in an independent cohort. JAK2 activating mutations occurred in 10/53 DS ALL cases (18.9%). Mutations were overrepresented in males (P < 0.03), occurred once in association with high hyperdiploidy and were not significantly correlated with age, initial white blood count, or event-free survival. Our results confirm the significance of JAK-STAT pathway activation in DS ALL.
authors.affiliation: Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Amos
authors.initials: A
authors.lastname: Gaikwad
authors.forename: Cassia L
authors.initials: CL
authors.lastname: Rye
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Karen R
authors.initials: KR
authors.lastname: Rabin
mesh_terms: D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D004171:Diploidy; D018572:Disease-Free Survival; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics / Q000401:mortality; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D017354:Point Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D053614:Janus Kinase 2