EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications

Blood. 2016 May 5;127(18):2214-8. doi: 10.1182/blood-2015-09-670166. Epub 2016 Feb 12.

Abstract

The EBF1-PDGFRB gene fusion accounts for <1% of B-cell precursor acute lymphoblastic leukemia (ALL) cases and occurs within the Philadelphia-like ALL subtype. We report 15 EBF1-PDGFRB-positive patients from childhood ALL treatment trials (ALL 97/99, UKALL 2003, UKALL 2011) in the United Kingdom. The fusion arose from interstitial deletion of 5q33 (n = 11), balanced rearrangement (n = 2), or complex rearrangement (n = 2). There was a predominance of females (n = 11), median age of 12 years, and median white blood cell count of 48.8 × 10(9)/L. Among 12 patients who achieved complete remission on earlier trials (ALL 97/99 and UKALL 2003), 10 were positive for minimal residual disease (MRD) at the end of induction, and 7 relapsed 18 to 59 months after diagnosis. The majority (9 of 12) remained alive 6 to 9 years after diagnosis. There are reports of EBF1-PDGFRB-positive patients who are refractory to conventional chemotherapy who achieve complete response when treated with the tyrosine kinase inhibitor imatinib. These findings have prompted screening for EBF1-PDGFRB in patients entered onto the current UKALL 2011 trial for whom induction therapy failed, who did not achieve remission by day 29, or who remained MRD positive (>0.5%) at week 14. Two UKALL 2011 patients, positive for EBF1-PDGFRB, received imatinib; 1 died 6 months after a matched unrelated bone marrow transplant as a result of undefined encephalopathy, and the other remained in remission 10 months after diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow Transplantation
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 5 / genetics
  • Combined Modality Therapy
  • Female
  • Humans
  • Imatinib Mesylate / therapeutic use
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor beta / genetics*
  • Remission Induction
  • Sequence Deletion
  • Trans-Activators / genetics*
  • Translocation, Genetic
  • Treatment Outcome
  • Young Adult

Substances

  • EBF1 protein, human
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Trans-Activators
  • Imatinib Mesylate
  • PDGFRB protein, human
  • Receptor, Platelet-Derived Growth Factor beta