title: Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation.
abstract: To study the role of the JAK2-V617F mutation in leukemic transformation, we examined 27 patients with myeloproliferative disorders (MPDs) who transformed to acute myeloid leukemia (AML). At MPD diagnosis, JAK2-V617F was detectable in 17 of 27 patients. Surprisingly, only 5 of 17 patients developed JAK2-V617F-positive AML, whereas 9 of 17 patients transformed to JAK2-V617F-negative AML. Microsatellite analysis in a female patient showed that mitotic recombination was not responsible for the transition from JAK2-V617F-positive MPD to JAK2-V617F-negative AML, and clonality determined by the MPP1 polymorphism demonstrated that the granulocytes and leukemic blasts inactivated the same parental X chromosome. In a second patient positive for JAK2-V617F at transformation, but with JAK2-V617F-negative leukemic blasts, we found del(11q) in all cells examined, suggesting a common clonal origin of MPD and AML. We conclude that JAK2-V617F-positive MPD frequently yields JAK2-V617F-negative AML, and transformation of a common JAK2-V617F-negative ancestor represents a possible mechanism.
authors.affiliation: Department of Research, Experimental Hematology, University Hospital Basel, Basel, Switzerland,
authors.forename: Alexandre
authors.initials: A
authors.lastname: Theocharides
authors.forename: Marjorie
authors.initials: M
authors.lastname: Boissinot
authors.forename: François
authors.initials: F
authors.lastname: Girodon
authors.forename: Richard
authors.initials: R
authors.lastname: Garand
authors.forename: Soon-Siong
authors.initials: SS
authors.lastname: Teo
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Pascaline
authors.initials: P
authors.lastname: Talmant
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hermouet
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D041321:Chromosomes, Human, X; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D016547:Kinesins; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D053614:Janus Kinase 2; C438388:KIF20B protein, human; D016547:Kinesins