title: Chronic myeloproliferative diseases with and without the Ph chromosome: some unresolved issues.
abstract: Ph-positive chronic myeloid leukemia (CML) and Ph-negative chronic myeloproliferative diseases (MPDs), characterized in many cases by the presence of the JAK2(V617F) mutation, have many features in common and yet also show fundamental differences. In this review, we pose five discrete and related questions relevant to both categories of hematological malignancy, namely: What are the mechanisms that underlie disease progression from a relatively benign or chronic phase? By what therapeutic methods might one target residual leukemia stem cells in CML? Is JAK2(V617F) the original molecular event in MPD? What epigenetic events must have a role in dictating disease phenotype in MPDs? And finally, Will the benefits conferred by current or future JAK2(V617F) inhibitors equal or even surpass the clinical success that has resulted from the use of tyrosine kinase inhibitors in CML? These and others questions must be addressed and in some cases should be answered in the foreseeable future.
authors.affiliation: Department of Haematology, Imperial College at Hammersmith Hospital, London W12 0NN, UK. jgoldman@imperial.ac.uk
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: A R
authors.initials: AR
authors.lastname: Green
authors.forename: T
authors.initials: T
authors.lastname: Holyoake
authors.forename: C
authors.initials: C
authors.lastname: Jamieson
authors.forename: R
authors.initials: R
authors.lastname: Mesa
authors.forename: T
authors.initials: T
authors.lastname: Mughal
authors.forename: F
authors.initials: F
authors.lastname: Pellicano
authors.forename: D
authors.initials: D
authors.lastname: Perrotti
authors.forename: R
authors.initials: R
authors.lastname: Skoda
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D002908:Chronic Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000145:classification / Q000235:genetics*; D010677:Philadelphia Chromosome
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2