RETRACTED ARTICLE: Association of BCR-ABL Alternative Splice Variants with Disease Progression, Treatment Response and Survival in Chronic Myeloid Leukemia Patients Treated with Firstline Imatinib Monotherapy

Full Length Research Article

RETRACTED ARTICLE: Association of BCR-ABL Alternative Splice Variants with Disease Progression, Treatment Response and Survival in Chronic Myeloid Leukemia Patients Treated with Firstline Imatinib Monotherapy

Nawaf Al-anazi1, Zafar Iqbal1,2,3, Tanveer Akhtar1, Ahmad M. Khalid3, Aamer Aleem4, Saba Shahzadi2, Afia M. Akram2,5, Mahmood Rasool6, Ijaz H. Shah7, Muhammad Khalid7, Mudassar Iqbal8, Abid Jameel9, Zeba Aziz10, 11, Muhammad Farooq Sabar12, Maryam AlMajed1, Buthinah AlShehab1, Sarah AlMukhaylid, Nouf AlMutairi, Dhay Almaghlouth1, Alhanoof Alsuwaidani1, Muhammad Arshad 13, Rashid Ayub14, Khaled AlJarrah1,15, Amer Mehmood16

Adv. life sci., vol. 9, no. 4, pp. 612-617, December 2022
*– Corresponding Author: Zafar Iqbal (Email: drzafar.medgen@yahoo.com)
Authors' Affiliations

 1. CoAMS-A, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City/KAIMRC, National Guard Health Affairs, Al-Ahsa – Saudi Arabia
2. Hematology, Oncology and Pharmaco-genetic Engineering Sciences (HOPES) Group, Health Sciences Department of Zoology, University of the Punjab, Lahore 54590 – Pakistan
3. Next-Generation Medical Biotechnology Division, Department of Biotechnology, University of Sialkot – Pakistan
4. Division of Hematology/Oncology, Department of Medicine, KKUH and College of Medicine, King Saud University, Riyadh – Saudi Arabia
5. University of Education Lahore, Pakistan
6. CEGMR, King Abdulaziz University, Jeddah – Saudi Arabia
7. Allied Hospital Faisalabad – Pakistan
8. Asian Medical Institute, Kant – Kyrgyzstan
9. Khyber Teaching Hospital and Hayatabad Medical Complex, Peshawar – Pakistan
10. Department of Oncology, Hamid Latif Hospital, Lahore – Pakistan
11. Department of Oncology, Jinnah Hospital, Lahore – Pakistan
12. Centre for Applied Molecular Biology, University of the Punjab, Lahore – Pakistan
13. Department of Biological Sciences, International Islamic University, Islamabad – Pakistan
14. Department of Science and Technology Innovation Unit (STIU), King Saud University, Riyadh – Saudi Arabia
15.  Jordan University of Science and Technology. Irbid – Jordan
16. Cancer Stem Cell Unit, Department of Anatomy, King Saud University, Riyadh – Saudi Arabia 

[Date Received: 04/01/2022; Date Revised: 09/01/2022; Date Published: 31/12/2022]

Important Note: This article was retracted on 20 July 2025.

Abstractaa download_button
Introduction
Methods
Results
Discussion
References 

Abstract

Background: Alternative RNA splicing has diverse biological effects in heath as well as disease. It also contributes to cancer onset and progression. Chronic Myeloid Leukemia (CML) results due to BCR-ABL fusion oncogene that is created due to chromosomal translocation t [9; 22] [q34; q11]). BCR-ABL is target of tyrosine kinase inhibitors (TKIs). BCR-ABL through alternative splicing can generate b2a2, b3a2 and some other rare splicing variants. BCR-ABL variants may vary in their response to TKI treatment and disease progression potential, which is a major factor contributing to dismal treatment outcome in CML. Objective: The objective of this study is to investigate correlation of BCR-ABL splice variants with TKI treatment outcome and survival in three phases of CML that has rarely been studied previously.

Methods: BCR-ABL splice variants were studied using reverse transcriptase PCR (RT-PCR). in 70 CML patients from three phases of CML who were receiving imatinib (TKI) treatment.

Results: Frequencies of different BCR/ABL splice variants like b3a2, b2a2 and b3a2+b2a2 were 49 (70%), 15 (21.4%) and 6 (8.6%), respectively. Splice variant b2a2 were more common (53.3%) in chronic phase CML (CP-CML) while b3a2 had higher frequency in advanced phases of CML (44.9%). CML patients with b2a2 transcript had better complete cytogenetic response and major molecular response to TKI treatment overall (100% vs. 24.5%) as well as in CP-CML (100% vs. 85.7%) and superior survival when compared to patients with b3a2 splice variant. All patients who died had male gender, less than 33 years age, b3a2 transcript, advanced phases of CML and imatinib resistance.

Conclusions: Splice variant b3a2 was associated with CML progression, poorer survival and inferior treatment outcome as compared to b2a2. Further investigations on BCR-ABL splice variants and their roles in CML pathogenesis can provide deeper insights into CML biology and new targets for BCR-ABL positive leukemia treatment.          

Keywords: CML; BCR-ABL splice variants; Progression; Survival; Treatment outcome      

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