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.

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.

• Authors: Shahid M Baba, Zafar A Shah, Arshad A Pandith, Dil-Afroze, Aleem Jan, Khurshid A Mir, Sheikh A Aziz, Zahoor Ahmad
• Journal: Cancer genetics (Cancer Genet) Vol. 231-232 Pg. 14-21 (02 2019) ISSN: 2210-7762 [Print] United States
• PMID: 30803552 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• 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, genetics)
• Male
• Middle Aged
• Multivariate Analysis
• Oncogene Proteins, Fusion (genetics)
• RNA, Messenger (genetics, metabolism)
• Treatment Outcome
• Tretinoin (therapeutic use)
• Young Adult