• POOJA KUSHWAH
• DR. PUSHPENDRA KUMAR*
• RANJEET KUMAR

ABSTRACT T-cell acute lymphoblastic leukaemia (T-ALL) is a formidable hematologic malignancy, noted for its aggressive clinical course and unfavourable prognosis. Nelarabine, a guanine nucleoside analog approved by the FDA in March 2023, has emerged as the sole T-ALL-specific therapeutic agent in clinical use. This compound preferentially accumulates in T-cells, where its active metabolite, ara-G triphosphate, disrupts DNA synthesis and induces apoptosis. Despite its increasing clinical application, a comprehensive understanding of nelarabine's molecular mechanisms and its effects on gene expression profiles in T-ALL remains incomplete. This literature review systematically explores the intracellular metabolism of nelarabine, the molecular pathways it influences, resistance mechanisms, and implications for optimizing therapeutic strategies. Evidence indicates that nelarabine-induced gene expression alterations involve dysregulation of DNA synthesis pathways, apoptotic machinery, and metabolic reprogramming. Emerging research suggests that resistance to nelarabine is associated with changes in drug transporters, phosphorylation enzymes, and anti-apoptotic signaling. Understanding these molecular mechanisms is crucial for identifying patient populations most likely to benefit from nelarabine-based therapy and for developing rational combination strategies to overcome resistance. This review synthesizes current knowledge on nelarabine's effects on T-ALL gene expression and proposes future research directions to enhance treatment efficacy.

Keywords: Nelarabine, T-cell acute lymphoblastic leukemia, gene expression, molecular mechanisms, drug resistance, ara-G triphosphate

"Impact of Nelarabine on Gene Expression Profiles in T-Cell Acute Lymphoblastic Leukaemia: A Comprehensive Literature ", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.12, Issue 11, page no.c177-c186, November-2025, Available :http://www.jetir.org/papers/JETIR2511221.pdf

"Impact of Nelarabine on Gene Expression Profiles in T-Cell Acute Lymphoblastic Leukaemia: A Comprehensive Literature ", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.12, Issue 11, page no. ppc177-c186, November-2025, Available at : http://www.jetir.org/papers/JETIR2511221.pdf