Clinical characteristics and prognostic significance of chronic myeloid leukemia with rare BCR-ABL1 transcripts

Leuk Lymphoma. 2019 Dec;60(12):3051-3057. doi: 10.1080/10428194.2019.1607329. Epub 2019 Jul 1.

Abstract

The prognostic significance of rare BCR-ABL1 transcripts is uncertain in the tyrosine kinase inhibitor (TKI) era. In this retrospective study, 40 (1.7%) patients with rare BCR-ABL1 transcripts were identified from a cohort of 2331 chronic myeloid leukemia (CML) patients; 4 types of rare transcripts were identified, including e1a2 (0.9%), e19a2 (0.4%), e13a3 (0.1%), and e14a3 (0.3%). Compared to patients with the typical transcript, those with the e1a2 transcript had an inferior response to TKIs and a worse outcome. Patients with the e19a2 transcript had a high rate of early optimal response to TKIs, but most of them later lost the complete cytogenetic response (CCyR) due to BCR-ABL1 mutations, resulting in a poor prognosis. Patients with the e13a3/e14a3 transcript responded well to TKIs and had a good outcome. These findings indicate that the type of BCR-ABL1 transcript should be considered when determining the treatment for CML patients in the TKI era.

Keywords: Chronic myeloid leukemia; cytogenetic response; prognosis; rare BCR-ABL1 transcripts; tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Child
  • Child, Preschool
  • Cytogenetic Analysis
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Frequency
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Middle Aged
  • Mutation
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Messenger*
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • BCR-ABL1 fusion protein, human
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Fusion Proteins, bcr-abl