Arshad Farah, Ali Amjad, Rehman Gauhar, Halim Sobia Ahsan, Waqas Muhammad, Khalid Asaad, Abdalla Ashraf N, Khan Ajmal, Al-Harrasi Ahmed
Molecular Virology Laboratory Centre for Applied Molecular Biology (CAMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore54590, Pakistan.
Department of Biotechnology and Genetic Engineering, Hazara University, Mansehra21120, Khyber Pakhtunkhwa, Pakistan.
ACS Omega. 2023 Jan 29;8(6):5975-5982. doi: 10.1021/acsomega.2c07885. eCollection 2023 Feb 14.
Leukemia is a proliferative disorder of myeloid and lymphoid cells that may lead to death. Different types of leukemia have been reported, and several genetic and environmental factors are involved in their development. The Philadelphia chromosome causes the most common mutation known as breakpoint cluster region-Abelson oncogene (BCR-ABL1), which shows abnormal protein tyrosine kinase (PTK) activity. Basically, this activity is accountable for activating multiple pathways, including the inhibition of cell differentiation, controlled proliferation, and cell death. As a result of the absence of kinase activity, this mutation leads to the uncontrolled proliferation of leukocytes, causing chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and chronic lymphocytic leukemia (CLL). This study aimed to evaluate the level of BCR-ABL1 expression in patients with these types of leukemias through qPCR. In brief, PBMCs were isolated from blood samples of patients, RNA was extracted from PBMCs, cDNA was synthesized, and the transcript levels of BCR-ABL1 in patients with each type of leukemia were determined by qPCR. The clinical, demographical, and experimental data were analyzed among CML, AML, and ALL patients. Results: The BCR-ABL1 expression levels are variable in all studied groups and are 90, 30-35, and 1-2.5% in CML, ALL, and AML, respectively. Demographic characteristics such as gender, BMI, age, family history, and clinical parameters along with CBC are also associated with the prevalence and diagnosis of leukemia. In a comparative expression analysis, the expression of BCR-ABL1 is onefold high in AML, but four- and sevenfold high in ALL and CML, respectively, as compared with normal levels. Conclusions: In this study, a significant difference was observed in the expression levels of BCR-ABL1 between CML ( = 0.0043) and ALL ( = 0.0006) and between CML and AML groups, and a high expression of BCR-ABL1 was noted in CML as compared with ALL and AML.
白血病是一种髓系和淋巴系细胞的增殖性疾病,可能导致死亡。已报道了不同类型的白血病,其发病涉及多种遗传和环境因素。费城染色体导致最常见的突变,即断裂簇区域-阿贝尔森癌基因(BCR-ABL1),该基因表现出异常的蛋白酪氨酸激酶(PTK)活性。基本上,这种活性负责激活多种途径,包括抑制细胞分化、控制增殖和细胞死亡。由于缺乏激酶活性,这种突变导致白细胞不受控制地增殖,引发慢性髓性白血病(CML)、急性髓性白血病(AML)、急性淋巴细胞白血病(ALL)和慢性淋巴细胞白血病(CLL)。本研究旨在通过定量聚合酶链反应(qPCR)评估这些类型白血病患者中BCR-ABL1的表达水平。简而言之,从患者的血液样本中分离出外周血单核细胞(PBMCs),从PBMCs中提取RNA,合成互补DNA(cDNA),并通过qPCR测定每种类型白血病患者中BCR-ABL1的转录水平。对CML、AML和ALL患者的临床、人口统计学和实验数据进行了分析。结果:在所有研究组中,BCR-ABL1的表达水平各不相同,在CML、ALL和AML中分别为90%、30%-35%和1%-2.5%。性别、体重指数(BMI)、年龄、家族史等人口统计学特征以及临床参数和全血细胞计数(CBC)也与白血病的患病率和诊断有关。在比较表达分析中,与正常水平相比,BCR-ABL1在AML中的表达高1倍,但在ALL和CML中分别高4倍和7倍。结论:在本研究中,观察到CML(P = 0.0043)与ALL(P = 0.0006)之间以及CML与AML组之间BCR-ABL1的表达水平存在显著差异,并且与ALL和AML相比,CML中BCR-ABL1表达较高。