Vasconcelos A P, Azevedo I F, Melo F C B C, Neves W B, Azevedo A C A C, Melo R A M
, , Brasil
, , Brasil.
Genet Mol Res. 2017 Apr 20;16(2):gmr-16-02-gmr.16029541. doi: 10.4238/gmr16029541.
In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.
在慢性髓性白血病(CML)中,BCR-ABL1基因重排可产生两种主要类型的信使核糖核酸(e14a2和e13a2)。由于结果相互矛盾,这些转录本的临床价值仍存在争议。本研究的目的是确定e14a2和e13a2转录本与实验室变量以及治疗反应之间的关联。本研究纳入了203例成年CML患者,这些患者在巴西东北部一家参考血液学中心接受伊马替尼作为一线药物治疗。在获得知情同意后获取临床和实验室数据。根据国际协议BIOMED-1收集样本用于RNA提取,并通过逆转录-聚合酶链反应(PCR)进行分析。采用2013年白血病网络标准来确定分子反应。BCR-ABL1转录本的频率分布为e14a2(64%)、e13a2(34%)和双阳性(2%)。结果显示,e14a2转录本类型与血小板增多症存在统计学显著关联(P = 0.0005),而e13a2与白细胞计数较高存在关联(P = 0.0491)。在44例患者的亚组中,通过定量PCR在3个月(BCR-ABL1≤10%)、6个月(BCR-ABL1≤1%)或12个月(BCR-ABL1≤0.1%)时评估对伊马替尼治疗的分子反应。尽管转录本为e14a2的患者显示出比转录本为e13a2的患者有更高的良好反应频率,但这种差异无统计学意义。与已发表的数据一致,我们的结果显示慢性髓性白血病患者中BCR-ABL1转录本e14a2与血小板增多症相关,BCR-ABL1转录本e13a2与白细胞增多症相关。