TY - JOUR
T1 - The saga of JAK2 mutations and translocations in hematologic disorders
T2 - pathogenesis, diagnostic and therapeutic prospects, and revised World Health Organization diagnostic criteria for myeloproliferative neoplasms
AU - Smith, Cristina A.
AU - Fan, Guang
PY - 2008/6
Y1 - 2008/6
N2 - JAK2 is a tyrosine kinase involved in cytokine signaling. The JAK2V617F point mutation, first described in 2005, results in constitutive activation of JAK2 and is now widely used as a diagnostic marker for Philadelphia chromosome negative myeloproliferative neoplasms. In recent years, more novel JAK2 mutations and fusion genes have been discovered in myeloproliferative neoplasms and other hematologic malignancies. This review aims to summarize the discovery and use of the JAK2V617F point mutation, other novel JAK2 mutations, and JAK2 translocations in diagnosing myeloproliferative neoplasms, acute myeloid leukemia, and acute lymphoid leukemia. JAK2 mutation testing is addressed, including the sensitivity and specificity of the different JAK2 mutation testing methods, clinical indications for use, and the use of quantitative JAK2 mutation testing for routine pathologic diagnosis, prognosis, and monitoring response to therapy. The relationship of JAK2 mutation to endogenous erythroid colony formation, thrombopoietin receptor mutation, polycythemia rubra vera-1 overexpression, and thrombopoietin receptor underexpression in myeloproliferative neoplasms are explored. Also discussed are the JAK2 inhibitors for clinical trials. Finally, the advantages of the newly proposed World Health Organization classification for myeloproliferative neoplasms are reviewed.
AB - JAK2 is a tyrosine kinase involved in cytokine signaling. The JAK2V617F point mutation, first described in 2005, results in constitutive activation of JAK2 and is now widely used as a diagnostic marker for Philadelphia chromosome negative myeloproliferative neoplasms. In recent years, more novel JAK2 mutations and fusion genes have been discovered in myeloproliferative neoplasms and other hematologic malignancies. This review aims to summarize the discovery and use of the JAK2V617F point mutation, other novel JAK2 mutations, and JAK2 translocations in diagnosing myeloproliferative neoplasms, acute myeloid leukemia, and acute lymphoid leukemia. JAK2 mutation testing is addressed, including the sensitivity and specificity of the different JAK2 mutation testing methods, clinical indications for use, and the use of quantitative JAK2 mutation testing for routine pathologic diagnosis, prognosis, and monitoring response to therapy. The relationship of JAK2 mutation to endogenous erythroid colony formation, thrombopoietin receptor mutation, polycythemia rubra vera-1 overexpression, and thrombopoietin receptor underexpression in myeloproliferative neoplasms are explored. Also discussed are the JAK2 inhibitors for clinical trials. Finally, the advantages of the newly proposed World Health Organization classification for myeloproliferative neoplasms are reviewed.
KW - Acute lymphoblastic leukemia
KW - Acute myeloid leukemia
KW - Chronic myeloproliferative disorder
KW - JAK2 mutation
KW - JAK2 translocation
KW - Lymphoma
KW - Myelodysplastic syndrome
KW - Myeloproliferative neoplasms
KW - WHO classification
UR - http://www.scopus.com/inward/record.url?scp=44449118424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44449118424&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2008.02.004
DO - 10.1016/j.humpath.2008.02.004
M3 - Article
C2 - 18538168
AN - SCOPUS:44449118424
SN - 0046-8177
VL - 39
SP - 795
EP - 810
JO - Human Pathology
JF - Human Pathology
IS - 6
ER -