Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene

Hon Fong L. Mark, Edgar A. Sotomayor, Marilu Nelson, Fernando Chaves, Warren G. Sanger, Zahid Kaleem, Samuel K. Caughron

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalExperimental and Molecular Pathology
Volume81
Issue number3
DOIs
StatePublished - Dec 1 2006

Fingerprint

Janus Kinase 2
Primary Myelofibrosis
Genes
Literature
Myeloproliferative Disorders
Fluorescence In Situ Hybridization
Cytogenetics
Chromosome Aberrations
Neoplasms
Bone
Blood
Bone Marrow
Therapeutics
ribophorin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene. / Mark, Hon Fong L.; Sotomayor, Edgar A.; Nelson, Marilu; Chaves, Fernando; Sanger, Warren G.; Kaleem, Zahid; Caughron, Samuel K.

In: Experimental and Molecular Pathology, Vol. 81, No. 3, 01.12.2006, p. 217-223.

Research output: Contribution to journalArticle

Mark, Hon Fong L. ; Sotomayor, Edgar A. ; Nelson, Marilu ; Chaves, Fernando ; Sanger, Warren G. ; Kaleem, Zahid ; Caughron, Samuel K. / Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene. In: Experimental and Molecular Pathology. 2006 ; Vol. 81, No. 3. pp. 217-223.
@article{77d438c7ac354d718861841f18a2e7ee,
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.",
author = "Mark, {Hon Fong L.} and Sotomayor, {Edgar A.} and Marilu Nelson and Fernando Chaves and Sanger, {Warren G.} and Zahid Kaleem and Caughron, {Samuel K.}",
year = "2006",
month = "12",
day = "1",
doi = "10.1016/j.yexmp.2006.07.004",
language = "English (US)",
volume = "81",
pages = "217--223",
journal = "Experimental and Molecular Pathology",
issn = "0014-4800",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Chronic idiopathic myelofibrosis (CIMF) resulting from a unique 3;9 translocation disrupting the janus kinase 2 (JAK2) gene

AU - Mark, Hon Fong L.

AU - Sotomayor, Edgar A.

AU - Nelson, Marilu

AU - Chaves, Fernando

AU - Sanger, Warren G.

AU - Kaleem, Zahid

AU - Caughron, Samuel K.

PY - 2006/12/1

Y1 - 2006/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33750497611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750497611&partnerID=8YFLogxK

U2 - 10.1016/j.yexmp.2006.07.004

DO - 10.1016/j.yexmp.2006.07.004

M3 - Article

C2 - 16959246

AN - SCOPUS:33750497611

VL - 81

SP - 217

EP - 223

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

SN - 0014-4800

IS - 3

ER -