Mutational status of myeloproliferative neoplasms.
Philadelphia negative myeloproliferative neoplasms include essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Altered signaling is a hallmark of myeloproliferative neoplasms, as demonstrated by the presence of activating JAK2 (V617F) mutation in about 70% of patients (95% of polycythemia vera, 50%-60% of essential thrombocythemia, and 50%-60% of primary myelofibrosis). How a unique point mutation can cause three different phenotypes remains to be clarified. The oncogenic potential of this mutation has been documented by mouse models, and different clinical studies have demonstrated an effect of mutant allele burden on phenotype. Mutant allele burden, in fact, directly correlates with hemoglobin value, leukocyte count, and, inversely, with platelet count. The molecular basis of JAK2 (V617F)-negative myeloproliferative neoplasms remains largely unexplained. Additional mutations in MPL, TET2, and CBL genes have been found in a small proportion of these patients. Implications of these mutations in the understanding of the pathogenesis of myeloproliferative neoplasms and in the clinical phenotype are discussed in this review.
Department of Oncology and Hematology, Division of Hematology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy 27100.
Elisa
E
Rumi
Chiara
C
Elena
Francesco
F
Passamonti
D000595:Amino Acid Sequence; D000818:Animals; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D002898:Chromosomes, Human, Pair 8; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D005091:Exons; D020440:Gene Duplication; D006801:Humans; D053614:Janus Kinase 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D009369:Neoplasms / Q000235:genetics*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics; D017384:Sequence Deletion
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D049308:Dioxygenases; C541081:TET2 protein, human; D050721:Proto-Oncogene Proteins c-cbl; D053614:Janus Kinase 2; C067419:CBL protein, human