title: CBL mutations do not frequently occur in paediatric acute myeloid leukaemia.
abstract: RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in paediatric AML is still unknown. We performed mutation analysis of 283 newly diagnosed and 33 relapsed paediatric AML cases. Only two mutant cases (0·7%) were identified in the newly diagnosed paediatric AML samples, of which one was MLL-rearranged. Both mutant cases showed CBL mRNA expression in the range of the non-mutated cases. Phosphorylated extracellular signal-regulated kinase (pERK) was not correlated with CBL protein expression (n = 11). In conclusion, we report a very low CBL mutation frequency in paediatric AML, which, together with the lack of difference in protein and mRNA expression, illustrates the limited role of CBL in paediatric AML.
authors.affiliation: Department of Paediatric Oncology/Haematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Coenen
authors.forename: Emma M C
authors.initials: EM
authors.lastname: Driessen
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.forename: Valerie
authors.initials: V
authors.lastname: de Haas
authors.forename: Eveline S J M
authors.initials: ES
authors.lastname: de Bont
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Susan T C J M
authors.initials: ST
authors.lastname: Arentsen-Peters
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Stam
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism
chemical_list: D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human