The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene

Marina Bousquet; Cathy Quelen; Véronique De Mas; Eliane Duchayne; Blandine Roquefeuil; Georges Delsol; Guy Laurent; Nicole Dastugue; Pierre Brousset

doi:10.1038/sj.onc.1208850

The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene

Oncogene. 2005 Nov 3;24(48):7248-52. doi: 10.1038/sj.onc.1208850.

Authors

Marina Bousquet¹, Cathy Quelen, Véronique De Mas, Eliane Duchayne, Blandine Roquefeuil, Georges Delsol, Guy Laurent, Nicole Dastugue, Pierre Brousset

Affiliation

¹ Inserm U563 CPTP and laboratoire de cytogénétique des hémopathies, CHU Purpan, Place Baylac, 31059 Toulouse Cedex, France.

PMID: 16091753
DOI: 10.1038/sj.onc.1208850

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.

Oncogene (2005) 24, 7248-7252. doi:10.1038/sj.onc.1208850; published online 8 August 2005.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Antibiotics, Antineoplastic / therapeutic use
Antimetabolites, Antineoplastic / therapeutic use
Antineoplastic Agents / therapeutic use
Autoantigens
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / genetics*
Chromosomes, Human, Pair 8*
Chromosomes, Human, Pair 9*
Cytarabine / therapeutic use
Fatal Outcome
Genetic Variation
Humans
Hydroxyurea / therapeutic use
Idarubicin / therapeutic use
In Situ Hybridization, Fluorescence
Janus Kinase 2
Karyotyping
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Male
Middle Aged
Oncogene Proteins, Fusion / genetics*
Open Reading Frames
Protein Structure, Tertiary
Protein-Tyrosine Kinases / chemistry
Protein-Tyrosine Kinases / genetics*
Proto-Oncogene Proteins / chemistry
Proto-Oncogene Proteins / genetics*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Secondary Prevention
Sequence Analysis, RNA
Translocation, Genetic*
Treatment Outcome

Substances

Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Autoantigens
Cell Cycle Proteins
Oncogene Proteins, Fusion
PCM1 protein, human
Proto-Oncogene Proteins
RNA, Messenger
Cytarabine
Protein-Tyrosine Kinases
JAK2 protein, human
Janus Kinase 2
Hydroxyurea
Idarubicin