From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms.
Our understanding of the genetic basis of myeloproliferative neoplasms began in 2005, when the JAK2 (V617F) mutation was identified in polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2 exon 12 and MPL exon 10 mutations were then detected in subsets of patients, and subclonal driver mutations in other genes were found to be associated with disease progression. Recently, somatic mutations in the gene CALR, encoding calreticulin, have been found in most patients with essential thrombocythemia or primary myelofibrosis with nonmutated JAK2 and MPL. The JAK-STAT pathway appears to be activated in all myeloproliferative neoplasms, regardless of founding driver mutations. These latter, however, have different effects on clinical course and outcomes. Thus, evaluation of JAK2, MPL, and CALR mutation status is important not only for diagnosis but also for prognostication. These genetic data should now also be considered in designing clinical trials.
Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy; and.
Mario
M
Cazzola
Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria.
Robert
R
Kralovics
D019046:Bone Marrow Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D037282:Calreticulin / Q000235:genetics*; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D014944:World Health Organization
D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2