Therapeutic effects of tyrosine kinase inhibitors and subtypes of BCR-ABL1 transcripts in Japanese chronic myeloid leukemia patients with three-way chromosomal translocations

Leuk Res. 2018 Feb:65:74-79. doi: 10.1016/j.leukres.2018.01.005. Epub 2018 Jan 3.

Abstract

We analyzed the clinical responses to thyrosine kinase inhibitors (TKIs) and the molecular and cytogenetic characteristics of 18 chronic myeloid leukemia (CML) patients with 3-way chromosomal translocations. The patients were 14 men and 4 women, aged 23-75 years (median 57 years). The Sokal risk was low in 12 patients, intermediate in 4 patients, and high in 2 patients. Newly identified translocation breakpoints were seen in 7 of the 18 patients. Three patients had the same breakpoints of t(9;22;11)(q34;q11.2;q23). The best responses to TKIs were partial cytogenic response (PCyR) in 2 patients, complete cytogenic response (CCyR) in 3 patients, molecular response (MR) 3.0 in 7 patients, MR 4.0 in 3 patients, and MR 4.5 or higher in 3 patients. A total of 66.7% of patients did not achieve MR 4.0 or higher. In 3 patients in whom TKIs resulted in MR 4.5 or higher for more than 2 years, TKI treatment was discontinued. However, all of them exhibited a loss of MR3.0, at 2, 6, and 20 months after the discontinuation of treatment, respectively, and TKI treatment needed to be restarted. According to Kaplan-Meier survival curve analysis, the overall survival (OS) was 100 months in 56% of the patients. The 60-months cumulative incidences of CCyR, MR3.0, MR4.0 and MR4.5 were 88.9%, 72.2%, 33.3%, and 16.7%, respectively. In the 11 analyzable patients, the BCR-ABL1 mRNA subtype was e14a2 type in 4 patients and e13a2 type in 7 patients.

Keywords: BCR-ABL1 transcripts; CML; Molecular biological effects; TKI; The best response; Three-way translocation.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Asian People / genetics*
  • Dasatinib / therapeutic use
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Japan
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / therapeutic use
  • RNA, Messenger / genetics*
  • Retrospective Studies
  • Translocation, Genetic*
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • BCR-ABL1 fusion protein, human
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • nilotinib
  • Dasatinib