title: Leukemic transformation in myeloproliferative neoplasms: therapy-related or unrelated?
abstract: Polycythemia vera, essential thrombocythemia, and primary myleofibrosis are chronic myeloproliferative neoplasms (MPNs) associated with an increased morbidity and mortality. MPNs are also associated with progression to acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The "true" rate of transformation is not known mainly due to selection bias in clinical trials and underreporting in population-based studies. The outcome after transformation is dismal. The underlying mechanisms of transformation are incompletely understood and in part remain an area of controversy. There is an intrinsic propensity in MPNs to progress to AML/MDS, the magnitude of which is not fully known, supporting a role for nontreatment-related factors. High doses of alkylating agents, P(32) and combined cytoreductive treatments undoubtedly increase the risk of transformation. The potential leukemogenic role of hydroxyurea has been a matter of debate due to difficulties in performing large prospective randomized trials addressing this issue. The main focus of this review is to elucidate therapy-related leukemic transformation in MPNs with a special focus on the role of hydroxyurea.
authors.affiliation: Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: magnus.bjorkholm@karolinska.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: malin.hultcrantz@ki.se.
authors.forename: Malin
authors.initials: M
authors.lastname: Hultcrantz
authors.affiliation: Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: asa.rangert-derolf@karolinska.se.
authors.forename: Åsa Rangert
authors.initials: ÅR
authors.lastname: Derolf
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000401:mortality; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000401:mortality; D010761:Phosphorus Radioisotopes / Q000627:therapeutic use; D011087:Polycythemia Vera / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D055728:Primary Myelofibrosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D010761:Phosphorus Radioisotopes; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea
keywords: JAK2 mutation; X-ray treatment; alkylators; antineoplastic agents; essential thrombocythemia; hydroxyurea; leukemia etiology; leukemic transformation; myeloproliferative neoplasm; polycythemia vera; primary myelofibrosis; radioactive phosphorous; risk factor