Influence of bcr-3 PML-RARα transcript on outcome in Acute Promyelocytic Leukemia patients of Kashmir treated with all-trans retinoic acid and/or arsenic tri-oxide

Cancer Genet. 2019 Feb:231-232:14-21. doi: 10.1016/j.cancergen.2018.12.003. Epub 2018 Dec 29.

Abstract

Aims: Distinct types of PML-RARα hybrid transcripts viz bcr-1, bcr-2 and bcr-3 result from translocation between chromosomes 15 and 17 t(15;17) in Acute Promyelocytic Leukemia patients. We aimed to determine the frequencies of the PML-RARα transcripts and FLT3-ITD mutations in APL patients to evaluate their prognostic implications and also to analyze their impact on disease outcome.

Main method: RT-PCR and Rq-PCR were adopted for transcript typing and quantitation of PML-RARα transcripts while FLT3-ITD was detected by PCR in APL patients.

Key findings: PML-RARα bcr-1, bcr-2 and bcr-3 transcripts were found in 26, 3 and 16 cases respectively. 64.4% patients achieved complete remission, 22.2% expired early wherein majority of the cases expressed bcr-3 transcript (p = 0.03). 50% relapse rate was observed in patients with bcr-3 transcripts. Multivariate analysis showed expression of bcr-3 transcript associated with early death (p = 0.027) and increased relapse risk (P = 0.046). Patients expressing bcr-3 hybrid transcript showed lowest OS of 28.0 months (± 5.26) (p = 0.027). FLT3-ITD mutation was detected in 5 (11.1%) patients and presence of these mutations was not associated either with PML-RARα transcripts or with disease outcome.

Significance: bcr-3 transcript has a more lethal outcome and is also associated with frequent relapse risk in APL patients of our region.

Keywords: ATRA; Acute Promyelocytic Leukemia; Arsenic Tri-Oxide; Kashmir; PML-RARα; Relapse; Remission.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arsenic Trioxide / therapeutic use*
  • Child
  • Chromosome Breakpoints*
  • Disease-Free Survival
  • Female
  • Humans
  • India
  • Kaplan-Meier Estimate
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Oncogene Proteins, Fusion / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Treatment Outcome
  • Tretinoin / therapeutic use*
  • Young Adult

Substances

  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Tretinoin
  • Arsenic Trioxide