bcr-3 PML-RARα转录本对克什米尔地区接受全反式维甲酸和/或三氧化二砷治疗的急性早幼粒细胞白血病患者预后的影响。

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.

作者信息

Baba Shahid M, Shah Zafar A, Pandith Arshad A, Jan Aleem, Mir Khurshid A, Aziz Sheikh A, Ahmad Zahoor

机构信息

Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar 190011, J&K, India.

出版信息

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

DOI:10.1016/j.cancergen.2018.12.003

PMID:30803552

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.

摘要

目的

急性早幼粒细胞白血病（APL）患者15号和17号染色体之间的易位t(15;17)会产生不同类型的PML-RARα融合转录本，即bcr-1、bcr-2和bcr-3。我们旨在确定APL患者中PML-RARα转录本和FLT3-ITD突变的频率，以评估其预后意义，并分析它们对疾病结局的影响。

主要方法

采用逆转录聚合酶链反应（RT-PCR）和实时定量聚合酶链反应（Rq-PCR）对APL患者的PML-RARα转录本进行分型和定量，同时通过聚合酶链反应检测FLT3-ITD。

主要发现

分别在26例、3例和16例患者中发现了PML-RARα bcr-1、bcr-2和bcr-3转录本。64.4%的患者实现完全缓解，22.2%的患者早期死亡，其中大多数病例表达bcr-3转录本（p = 0.03）。bcr-3转录本的患者复发率为50%。多因素分析显示，bcr-3转录本的表达与早期死亡相关（p = 0.027），且复发风险增加（P = 0.046）。表达bcr-3融合转录本的患者总生存期最短，为28.0个月（±5.26）（p = 0.027）。在5例（11.1%）患者中检测到FLT3-ITD突变，这些突变的存在与PML-RARα转录本或疾病结局均无关联。