Myeloid/lymphoid neoplasms with FGFR1 rearrangement

Leuk Lymphoma. 2018 Jul;59(7):1672-1676. doi: 10.1080/10428194.2017.1397663. Epub 2017 Nov 9.

Abstract

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL. Overall response rate to frontline therapy was 69%, and 76% of patients subsequently received allogeneic stem cell transplant (ASCT). After a median follow-up of 11 months, median progression-free survival was 15 months and median overall survival was not reached. In conclusion, FGFR1-rearranged hematologic malignancies present with features of MPN and/or AL. FGFR1 and RUNX1 are therapeutic targets for ongoing and future clinical trials.

Keywords: FGFR1 rearrangement; Myeloproliferative neoplasm; RUNX1; acute leukemia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Biomarkers, Tumor*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Gene Rearrangement*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Karyotype
  • Leukemia, Lymphoid / diagnosis
  • Leukemia, Lymphoid / genetics*
  • Leukemia, Lymphoid / mortality
  • Leukemia, Lymphoid / therapy
  • Lymphoma / diagnosis
  • Lymphoma / genetics*
  • Lymphoma / mortality
  • Lymphoma / therapy
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / mortality
  • Myeloproliferative Disorders / therapy
  • Prognosis
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Translocation, Genetic*
  • Young Adult

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1