Impact of the Major BCR-ABL1 Transcript Type on Clinical and Biological Parameters and Molecular Response in Patients With Chronic Myeloid Leukemia.

Q1 Medicine

Hematology/ Oncology and Stem Cell Therapy Pub Date : 2022-06-01 DOI:10.1016/j.hemonc.2020.08.003

Mourad Nachi, Ibtissem Kihel, Badra Entasoltane, Mohamed Brahimi, Nabil Yafour, Djaoued Guella, Amine Abed, Mohamed A Bekadja

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引用次数: 4

Abstract

Aim: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy.

Methods: This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR and quantification of transcripts by real-time quantitative PCR (qRT-PCR). The cumulative incidence of deep molecular response (DMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant.

Results: 61% of patients expressed b3a2, 35.82% b2a2 and 2.98% expressed a rare transcript of type e19a2. At diagnosis, the b2a2 type had a higher level of expression than that of b3a2 (67.92 vs 53.79%; P = 0.03). This insignificant difference between the two transcript subgroups was also observed for rates below 1% at 6 months (54 vs 39; P = 0.26) and below 0.1% (54 vs 44 %; P = 0.50), (77 vs 50%; P = 0.09) and (81 vs 78 %; P = 0.52) at 12, 18 and 24 months respectively. The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2. At 18 months post IM therapy, patients with a b3a2 transcript have a trend of better MMR that those with b2a2 (77 vs 50%; P = 0.09). The DMR was not significantly different between two groups at 24 months (50 vs 32%; P = 0.20) and 36 months (75 vs 70%; P = 0.54) respectively. The cumulative probability of achieving MRD at 5 years was higher in patients with b3a2 type but not statistically significant; (85 vs. 68%; P = 0.17).

Conclusion: Patients with b3a2 transcript may be associated with a better response to Imatinib therapy.

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BCR-ABL1主要转录类型对慢性髓性白血病患者临床和生物学参数及分子反应的影响

目的:在慢性髓性白血病(CML)中，MBCR-ABL1主要转录物类型对疾病表型和治疗反应的影响至今仍存在争议。本研究旨在研究Mb3a2和Mb2a2转录本对伊马替尼作为一线治疗的慢性期慢性髓性白血病(CP-CML)患者临床生物学参数和分子反应的影响。方法:该研究于2013年3月1日开始，为期6年。67例新发CP-CML患者采用伊马替尼作为一线治疗。收集所有患者的临床和生物学特征。分子分型采用多重RT-PCR，转录本定量采用实时定量PCR (qRT-PCR)。用Kaplan-Meier法估计深度分子反应(deep molecular response, DMR)的累积发生率。采用参数Log-Rank检验进行比较。P≤0.05为显著性。结果:61%的患者表达b3a2, 35.82%的患者表达b2a2, 2.98%的患者表达罕见的e19a2型转录本。诊断时，b2a2型表达水平高于b3a2型(67.92% vs 53.79%;P = 0.03)。在6个月时，两个转录亚组的发生率低于1%时也观察到这种不显著的差异(54 vs 39;P = 0.26)和低于0.1% (54% vs 44%;P = 0.50)， (77 vs 50%;P = 0.09)和(81% vs 78%;P = 0.52)，分别在12、18和24个月。这两种类型的转录物具有几乎相同的动力学。然而，BCR-ABL1/ABL比值下降的绝对值在表达b3a2的患者组中比表达b2a2的患者要快。在IM治疗后18个月，b3a2转录本患者的MMR趋势优于b2a2患者(77% vs 50%;P = 0.09)。两组患者在24个月时的DMR无显著差异(50% vs 32%;P = 0.20)和36个月(75% vs 70%;P = 0.54)。b3a2型患者在5年达到MRD的累积概率较高，但无统计学意义;(85比68%;P = 0.17)。结论:携带b3a2转录本的患者可能对伊马替尼治疗有更好的反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hematology/ Oncology and Stem Cell Therapy Medicine-Hematology

CiteScore

4.30

自引率

0.00%

发文量

审稿时长

27 weeks

期刊介绍： Hematology Oncology and Stem Cell Therapy is an international, peer-reviewed, open access journal that provides a vehicle for publications of high-quality clinical as well as basic science research reports in hematology and oncology. The contents of the journal also emphasize the growing importance of hematopoietic stem cell therapy for treatment of various benign and malignant hematologic disorders and certain solid tumors.The journal prioritizes publication of original research articles but also would give consideration for brief reports, review articles, special communications, and unique case reports. It also offers a special section for clinically relevant images that provide an important educational value.