Evaluating role of TNF-α in Tyrosine kinase Inhibitors-treated Chronic Myeloid Leukemia"

GRATIAL THERES JOSEPH¹Sandeep Kumar Swain¹Himanshu Dhanda¹Neetu Kushwaha¹Priti Kumari¹Mahek Pravin Kushalani¹Rakesh Kumar¹Baseer Noor²Sufian Zaheer²Aditi Jain²Ankur Jain²Sumita Chaudhry²PRANAY TANWAR³Amitabh Singh²Aroonima Misra^1*Bhavika Rishi^1*

• ¹Indian Council of Medical Research (ICMR), New Delhi, India
• ²Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
• ³All India Institute of Medical Sciences New Delhi, New Delhi, India

Abstract Purpose: Chronic Myeloid Leukemia (CML) is characterized by the BCR-ABL1 fusion gene and is effectively managed with tyrosine kinase inhibitors (TKIs). However, therapeutic resistance and the persistence of leukemic stem cells pose challenges to achieving long-term remission. Tumor Necrosis Factor-alpha (TNF-α), a pro-inflammatory cytokine, is implicated in leukemogenesis and resistance, yet its clinical relevance in Indian CML cohorts remains underexplored. Objective: This study investigates the pharmacodynamic and prognostic role of serum TNF-α levels in chronic-phase CML patients receiving first-line imatinib, aiming to evaluate its utility as a biomarker for treatment response. Methods: We conducted a prospective observational study on 40 CML patients treated at Safdarjung Hospital, New Delhi. Blood samples were taken before treatment and 5–7 months after starting imatinib. ELISA was used to quantify TNF-α levels, and qRT-PCR was used to monitor BCR-ABL1 transcripts. We analysed clinical and hematologic parameters using appropriate statistical methods. Results: Imatinib treatment significantly reduced serum TNF-α (259.5 to 129.8 pg/mL; p < 0.0001), mirroring the observed decrease in BCR-ABL1 transcripts. Basically, if TNF-α stuck around (r = 0.87), patients responded poorly, whereas good outcomes correlated with its quicker clearance (r = 0.45). Conclusion: Our data suggest that TNF-α represents a clinically relevant pharmacodynamic and prognostic biomarker for patients with chronic-phase CML receiving imatinib therapy. A decline in TNF-α levels was associated with a favorable therapeutic outcome, whereas failure of TNF-α to decline was indicative of an inferior outcome. TNF-α does not replace qRT-PCR–based monitoring of BCR-ABL1; however, it may be useful as an adjunctive prognostic marker, especially in resource-poor environments, pending appropriate prospective confirmation.