Myeloid neoplasms with eosinophilia

Blood. 2017 Feb 9;129(6):704-714. doi: 10.1182/blood-2016-10-695973. Epub 2016 Dec 27.

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 of PDGFRA, PDGFRB, or FGFR1, or with PCM1-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 of PDGFRA- and PDGFRB-rearranged neoplasms has been dramatically altered by imatinib. In contrast, patients with FGFR1 and JAK2 fusion 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 of FLT3 or ABL1 (eg, both of which commonly partner with ETV6), 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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Eosinophilia / diagnosis
  • Eosinophilia / genetics
  • Eosinophilia / pathology
  • Eosinophilia / therapy*
  • Gene Expression Regulation, Neoplastic*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Hypereosinophilic Syndrome / diagnosis
  • Hypereosinophilic Syndrome / genetics
  • Hypereosinophilic Syndrome / pathology
  • Hypereosinophilic Syndrome / therapy*
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Leukemia / diagnosis
  • Leukemia / genetics
  • Leukemia / pathology
  • Leukemia / therapy*
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology
  • Myeloproliferative Disorders / therapy*
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-abl / antagonists & inhibitors
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Transplantation, Homologous
  • fms-Like Tyrosine Kinase 3

Substances

  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • FGFR1 protein, human
  • FLT3 protein, human
  • PDGFRB protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
  • fms-Like Tyrosine Kinase 3
  • JAK2 protein, human
  • Janus Kinase 2
  • Proto-Oncogene Proteins c-abl

Supplementary concepts

  • Pdgfra-Associated Chronic Eosinophilic Leukemia