The integration of molecular diagnostics into routine clinical practice has fundamentally transformed the management of acute leukemias over the past decade. Next-generation sequencing technologies have enabled comprehensive genomic profiling that refines prognostic stratification, guides selection of targeted therapies, and enables monitoring of measurable residual disease. This review synthesizes current evidence on the role of molecular diagnostics in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), focusing on clinically relevant genetic alterations including FLT3, IDH1/2, NPM1, KMT2A rearrangements, and Philadelphia chromosome-like ALL. We examine how molecular findings inform risk stratification according to European LeukemiaNet guidelines, predict response to targeted inhibitors, and identify resistance mechanisms. Additionally, we discuss practical considerations for implementing molecular testing in clinical workflows, including optimal specimen types, testing platforms, turnaround time requirements, and interpretation of results by molecular tumor boards. Finally, we explore emerging applications of liquid biopsy for disease monitoring and early detection of relapse. As the therapeutic armamentarium expands, seamless integration of molecular diagnostics into clinical decision-making is essential to deliver precision medicine and improve outcomes for patients with acute leukemia.
Gamal Abdul Hamid1,2, Muna Yassin2, Thana Alsagaf2 (Sat,) studied this question.