title: Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene.
abstract: We report a case of t(3;9)(q21;p24) in a patient with chronic idiopathic myelofibrosis (CIMF), a chronic myeloproliferative disorder (CMPD), initially detected by G-banding and fluorescent in situ hybridization (FISH) in an unstimulated culture of peripheral blood. Subsequent cytogenetic studies of bone marrow aspirates showed the presence and persistence of the same translocation. No additional cytogenetic abnormalities were found. This appears to be a unique translocation that has not been previously reported in the English literature, although both breakpoints, 3q21 and 9p24, are well known cancer-related breakpoints. The former is the mapped location of the ribophorin 1 (RPN1) gene, whereas the latter is the mapped location of the janus kinase 2 (JAK2) gene. This raises the possibility that disruption of one or both loci at the breakpoints of the presently described structural chromosomal rearrangement may be the primary event leading to the initiation and development of the hematopoietic disorder in this patient. It is not unreasonable to hypothesize that the juxtaposition of the RPN1 gene on 3q21 with the JAK2 gene on 9p24 leads to enhanced JAK2 activity. Additional studies will be needed to provide further support for or to disprove this hypothesis. To the best of our knowledge, this is the first reported case of CIMF associated with a reciprocal 3;9 translocation with the 3q21 and 9p24 breakpoints. The elucidation of the mechanism of leukemogenesis in CIMF may one day lead to successful targeted therapy in this hematopoietic disorder. It may also shed additional light on the diagnosis, prognosis and treatment of certain other cancers with similar genetic etiologies.
authors.affiliation: Cytogenetics Laboratory, Center for Human Genetics, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Hon Fong L
authors.initials: HF
authors.lastname: Mark
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Sotomayor
authors.forename: Marilu
authors.initials: M
authors.lastname: Nelson
authors.forename: Fernando
authors.initials: F
authors.lastname: Chaves
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.forename: Zahid
authors.initials: Z
authors.lastname: Kaleem
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Caughron
mesh_terms: D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2 / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D053614:Janus Kinase 2