title: Myeloid neoplasms with eosinophilia.
abstract: Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, "Myeloid/lymphoid neoplasms with eosinophilia and rearrangement ofPDGFRA,PDGFRB, orFGFR1, or withPCM1-JAK2" In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed-phenotype leukemias or lymphomas. Eosinophilia is a common, but not invariable, feature of these diseases. The natural history ofPDGFRA- andPDGFRB-rearranged neoplasms has been dramatically altered by imatinib. In contrast, patients withFGFR1andJAK2fusion TK genes exhibit a more aggressive course and variable sensitivity to current TK inhibitors, and in most cases, long-term disease-free survival may only be achievable with allogeneic hematopoietic stem cell transplantation. Similar poor prognosis outcomes may be observed with rearrangements ofFLT3orABL1(eg, both of which commonly partner withETV6), and further investigation is needed to validate their inclusion in the current WHO-defined group of eosinophilia-associated TK fusion-driven neoplasms. The diagnosis chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) is assigned to patients with MPN with eosinophilia and nonspecific cytogenetic/molecular abnormalities and/or increased myeloblasts. Myeloid mutation panels have identified somatic variants in patients with a provisional diagnosis of hypereosinophilia of undetermined significance, reclassifying some of these cases as eosinophilia-associated neoplasms. Looking forward, one of the many challenges will be how to use the results of molecular profiling to guide prognosis and selection of actionable therapeutic targets.
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.affiliation: Division of Hematology, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004802:Eosinophilia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C496348:FGFR1 protein, human; C497970:FLT3 protein, human; C000605860:PDGFRB protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D051941:fms-Like Tyrosine Kinase 3; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D016315:Proto-Oncogene Proteins c-abl