Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.

ABSTRACTSmall molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the BCR::ABL1 kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to BCR::ABL1 dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight BCR::ABL1-dependent mechanisms of TKI resistance by reviewing clinically-documented BCR::ABL1 mutations and their consequences for TKI binding. In addition, we summarize BCR::ABL1 independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies.

Epidemiology of musculoskeletal complaints and diseases in Qatar: A cross-sectional study.

BACKGROUND: Musculoskeletal (MSK) conditions are considered a significant public health problem on account of their high prevalence in communities worldwide and their pervasive impact. Knowledge of the epidemiology of MSK symptoms and diseases is lacking in Qatar. Obtaining this information will guide local health policymakers in the future strategic planning of the health budget. OBJECTIVE: To estimate the prevalence rate of MSK disorders in the Qatari population above 15 years of age using the Community Oriented Program for the Control of Rheumatic Disease (COPCORD) survey. METHODS: This cross-sectional study targeted 1000 Qatari participants, including 500 males and 500 females. A door-to-door survey was conducted using the Arabic version of the COPCORD questionnaire with the help of research assistants. Participants with positive surveys were asked to visit Hamad General Hospital Rheumatology outpatient clinics for clinical evaluation by a rheumatologist. When necessary, laboratory testing and X-rays were conducted to confirm any MSK diagnosis. RESULTS: A total of 1239 (males, 50.8%) Qatari individuals randomly selected from the different municipalities of Qatar completed the COPCORD survey. Among the participants, 563 (45.4%) screened positive for MSK pain. Knee pain (24.5%) and back pain (23.3%) were the most common sites of pain, and both conditions showed no gender predominance (p = 0.073 and 0.108, respectively). Shoulder, wrist, hand, hip, and neck pain were significantly predominant in females (p < 0.001 for all). A total of 237 MSK disorders were diagnosed in 196 (15.8%) participants, including 181 degenerative joint diseases, 52 soft-tissue rheumatism conditions, and 4 autoimmune inflammatory disorders. Among degenerative joint diseases, knee osteoarthritis (6.4%) was the most common. Among soft-tissue rheumatic conditions, muscular lower back pain (1.9%), myofascial neck pain (0.64%), generalized body pain (0.32%), and shoulder tendinitis (0.7%) were the most common diseases. The autoimmune inflammatory disorders identified included rheumatoid arthritis (n = 2), connective tissue disease (n = 1), and inflammatory bowel disease-associated arthritis (n = 1). CONCLUSION: The overall prevalence rate of MSK disorders in this small cross-sectional cohort of Qatari individuals was 15.8%. Knee pain (24.5%) and knee osteoarthritis (6.4%) were the most common MSK complaints and diagnosis in the studied Qatari population. This study guides future efforts directed toward the prevention and management of MSK diseases. Further studies with a larger sample size are needed to verify the findings.