title: DNA copy number alterations mark disease progression in paediatric chronic myeloid leukaemia.
abstract: Early recognition of children with chronic phase chronic myeloid leukaemia (CML-CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because therapy options in CML-LyBC are limited. We used Multiplex Ligation-dependent Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy number alterations (CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected in CML-CP and may be used to predict disease progression to LyBC. CNAs were detected in all patients with CML-LyBC, but in none of the 77 patients with CML-CP. Based on this study we conclude that CNAs remain a hallmark of disease progression.
authors.affiliation: Division of Paediatric Oncology/Haematology, Department of Paediatrics, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Naomi E
authors.initials: NE
authors.lastname: van der Sligte
authors.forename: Manuela
authors.initials: M
authors.lastname: Krumbholz
authors.forename: Agata
authors.initials: A
authors.lastname: Pastorczak
authors.forename: Blanca
authors.initials: B
authors.lastname: Scheijen
authors.forename: Josephine T
authors.initials: JT
authors.lastname: Tauer
authors.forename: Christina
authors.initials: C
authors.lastname: Nowasz
authors.forename: Edwin
authors.initials: E
authors.lastname: Sonneveld
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Tiny G J
authors.initials: TG
authors.lastname: Meeuwsen-de Boer
authors.forename: Simon
authors.initials: S
authors.lastname: van Reijmersdal
authors.forename: Roland P
authors.initials: RP
authors.lastname: Kuiper
authors.forename: Jutta
authors.initials: J
authors.lastname: Bradtke
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.forename: Evelina S J M
authors.initials: ES
authors.lastname: de Bont
authors.forename: Frank N
authors.initials: FN
authors.lastname: van Leeuwen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001752:Blast Crisis / Q000235:genetics; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D009363:Neoplasm Proteins / Q000235:genetics; D017354:Point Mutation; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C497239:IKZF1 protein, human; D009363:Neoplasm Proteins; D051740:Ikaros Transcription Factor
keywords: IKZF1; copy number alterations; lymphoid blast crisis; paediatric CML