Comparative Expression Analysis of Breakpoint Cluster Region-Abelson Oncogene in Leukemia Patients

Farah Arshad; Amjad Ali; Gauhar Rehman; Sobia Ahsan Halim; Muhammad Waqas; Asaad Khalid; Ashraf N Abdalla; Ajmal Khan; Ahmed Al-Harrasi

doi:10.1021/acsomega.2c07885

Comparative Expression Analysis of Breakpoint Cluster Region-Abelson Oncogene in Leukemia Patients

ACS Omega. 2023 Jan 29;8(6):5975-5982. doi: 10.1021/acsomega.2c07885. eCollection 2023 Feb 14.

Authors

Farah Arshad¹, Amjad Ali^{2

1}, Gauhar Rehman³, Sobia Ahsan Halim⁴, Muhammad Waqas^{2

4}, Asaad Khalid^{5

6}, Ashraf N Abdalla⁷, Ajmal Khan⁴, Ahmed Al-Harrasi⁴

Affiliations

¹ Molecular Virology Laboratory Centre for Applied Molecular Biology (CAMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore54590, Pakistan.
² Department of Biotechnology and Genetic Engineering, Hazara University, Mansehra21120, Khyber Pakhtunkhwa, Pakistan.
³ District Medical Specialist Category-D Hospital Talash Dir Lower, Lower Dir23120, Khyber Pakhtunkhwa, Pakistan.
⁴ Natural and Medical Sciences Research Center, University of Nizwa, Birkat-Al-Mouz, 616, P.O. Box 33, Nizwa616, Sultanate of Oman.
⁵ Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Jazan45142, Saudi Arabia.
⁶ Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P.O. Box 2404, Khartoum11111, Sudan.
⁷ Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah21955, Saudi Arabia.

Abstract

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 (p = 0.0043) and ALL (p = 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.