Association Of BCR-ABL Alternative Splice Variants with Disease Progression, Treatment Response and Survival in Chronic Myeloid Leukemia Patients Treated with Firstline imatinib Monotherapy

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 

A Snapshot of the Experience of Dietitians during the COVID-19 Crisis in Five Arab Countries: Findings from a Regional Cross-Sectional Study

COVID-19’s intimidating spread has challenged the resilience of the global health systems, causing shifts in the practices of healthcare workers, including dietitians. The current study aimed to assess the change in dietitians’ practices and duties in hospitals/clinics after the commencement of COVID-19 pandemic. This cross-sectional study was conducted in five Arab countries between November 2020 and January 2021. A convenient sample of 903 dietitians filled an online self-administered questionnaire to meet the study aims. Nearly 40.0% of the dietitians experienced a change in their workload and caseload during the pandemic. Besides, 18.7% of the dietitians had been assigned additional tasks in their facilities. Nearly half the dietitians (46.9%) had started giving remote nutrition consultations, associated with a 21% drop in the number of dietitians offering in-person consultations (p = 0.001). Approximately 58.9% of the dietitians provided nutrition care to COVID-19 patients, with 48.4% having access to personal protective equipment. Moreover, 17.0% of dietitians supported COVID-19 patients with enteral and parenteral nutrition. In addition, 45.0% of dietitians reported that managing COVID-19 was challenging given that it was a newly discovered condition