title: The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene.
abstract: Several tyrosine kinase genes are involved in chromosomal translocations in chronic myeloproliferative disorders, but there are still uncharacterized translocations in some cases. We report two such cases corresponding to atypical chronic myeloid leukaemia with a t(8;9)(p22;p24) translocation. By fluorescence in situ hybridisation (FISH) on the corresponding metaphases with a bacterial artificial chromosome probe encompassing the janus kinase 2 (JAK2) gene at 9p24, we observed a split for both patients, suggesting that this gene was rearranged. The locus at 8p22 contains different candidate genes including the pericentriolar material 1 gene (PCM1), already implicated in reciprocal translocations. The rearrangement of the PCM1 gene was demonstrated by FISH, for both patients. By RT-PCR, we confirmed the fusion of 3' part of JAK2 with the 5' part of PCM1. Sequence analysis of the chimeric PCM1-JAK2 mRNA suggests that the putative protein displays the coiled-coil domains of PCM1 and the tyrosine kinase domain of JAK2. This new translocation identifies JAK2 as a possible therapeutic target for compounds with anti-tyrosine kinase activity.
authors.affiliation: Inserm U563 CPTP and laboratoire de cytogénétique des hémopathies, CHU Purpan, Place Baylac, 31059 Toulouse Cedex, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Bousquet
authors.forename: Cathy
authors.initials: C
authors.lastname: Quelen
authors.forename: Véronique
authors.initials: V
authors.lastname: De Mas
authors.forename: Eliane
authors.initials: E
authors.lastname: Duchayne
authors.forename: Blandine
authors.initials: B
authors.lastname: Roquefeuil
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001324:Autoantigens; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D003561:Cytarabine / Q000627:therapeutic use; D017809:Fatal Outcome; D014644:Genetic Variation; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D015255:Idarubicin / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055502:Secondary Prevention; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001324:Autoantigens; D018797:Cell Cycle Proteins; D015514:Oncogene Proteins, Fusion; C086074:PCM1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003561:Cytarabine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea; D015255:Idarubicin