Precision medicine in acute lymphoblastic leukemia: A narrative review of current strategies and future directions

Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous hematologic malignancy and the most common cancer in children, with significant morbidity and mortality in adults. Advances in molecular diagnostics and targeted therapies have shifted treatment from uniform chemotherapy toward precision medicine approaches tailored to individual genomic and clinical profiles. To summarize these approaches, a narrative review was conducted following the Scale for the Assessment of Narrative Review Articles (SANRA). A comprehensive literature search was performed in PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published between January 2015 and August 2026. Additional sources, including reference lists and clinical trial registries, were screened. Studies were selected based on relevance to precision medicine in ALL, including molecular diagnostics, pharmacogenomics, targeted therapy, and immunotherapy. Evidence was synthesized narratively without formal quality scoring. Key findings indicate that advances in next-generation sequencing have enabled the identification of clinically relevant molecular subtypes, including BCR-ABL1–positive, Philadelphia chromosome–like, and KMT2A-rearranged ALL, facilitating risk stratification and targeted treatment selection. Pharmacogenomic testing, particularly for TPMT and NUDT15 variants, supports individualized thiopurine dosing and reduces treatment-related toxicity. Targeted therapies and immunotherapies, including tyrosine kinase inhibitors, blinatumomab, inotuzumab ozogamicin, chimeric antigen receptor (CAR) T-cell therapy, and menin inhibition with revumenib for selected relapsed or refractory KMT2A-rearranged acute leukemias, have significantly improved outcomes in relapsed and refractory ALL. However, variability in access to molecular diagnostics, lack of standardized biomarker panels, and limited long-term outcomes data remain key challenges. Overall, Precision medicine is transforming the management of ALL by enabling individualized, biomarker-driven treatment strategies that improve survival and reduce toxicity. Broader implementation will require standardized diagnostic approaches, improved access to advanced therapies, and integration of real-world evidence to support clinical decision-making.