title: JAK2(V617F) mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones.
abstract: The 2008 World Health Organization (WHO) proposed revision of the classification of MDS recognizes a deletion (5q) subtype with mutation of Janus kinase-2 (JAK2(V617F)). We investigated the clonal origin of this gene mutation in a patient with del(5q) MDS presenting with thrombocytosis and normal hemoglobin. Analysis of colony forming units-granulocyte-monocyte (CFU-GM) and erythropoietin-independent growth of bone marrow (BM) and peripheral blood (PB) burst forming units-erythroid (BFU-E) showed that del(5q) and JAK2(V617F) existed in progenitors derived from independent clones. Fifty percent of endogenous erythroid colonies (EEC) harbored the JAK2(V617F) mutation whereas fluorescent in situ hybridization (Fish) with a chromosome 5 (q31.1) probe showed only a diploid allele compliment. Assessment of transcriptional clonality by iduronate-2-sulfatase (IDS) gene polymorphism suggested that JAK2(V617F) was acquired in at least two independent multipotent stem cell progeny. Our findings indicate that JAK2(V617F) mutant clones may arise in genetically discordant clones independent of del(5q).
authors.affiliation: Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL 33612, USA. Lubomir.Sokol@moffitt.org
authors.forename: L
authors.initials: L
authors.lastname: Sokol
authors.forename: G
authors.initials: G
authors.lastname: Caceres
authors.forename: K
authors.initials: K
authors.lastname: Rocha
authors.forename: K J
authors.initials: KJ
authors.lastname: Stockero
authors.forename: D W
authors.initials: DW
authors.lastname: Dewald
authors.forename: A F
authors.initials: AF
authors.lastname: List
mesh_terms: D019943:Amino Acid Substitution; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology*; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D010649:Phenylalanine / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D010649:Phenylalanine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D014633:Valine