Acute Promyelocytic Leukemia (APL), a rare subclass of hematological disorder of Acute Myeloid Leukemia, is distinguished due to the existence of promyelocytic leukemia with retinoic acid receptor (PML-RARα) fusion protein. These fusion proteins will disturb and manipulate the normal cell differentiation of leukocytes and will navigate the leukemogenesis. The commencement of target therapies like All-Trans Retinoic acid in combination with arsenic trioxide has drastically altered the treatment prospects regarding APL, handing over extraordinary remissions and better survival outcomes to the medical world. Biotechnological advancement has elucidated the molecular details of the disease which has helped in the creation and development of novel diagnostic tools and therapeutic strategies. Collective actions of ATRA and ATO will disintegrate the PML-RARα fusion protein, will induce apoptosis and will restore normal cell differentiation, thereby bringing out the importance of blending medicines in treatment and targeted therapies in APL management. Over and above, medical biotechnology has unlocked genomic and proteomic assessment and evaluation and uncovered new genetic aberrations and pathways with APL. This study also addresses treatment difficulties like relapse and therapeutic resistance, calling attention to the need for more innovative approaches using biotechnology. Biotechnology has lifted APL therapeutic management to a new high standard for targeted therapies in blood-related cancers by integrating molecular biology with clinical applications. © 2025 Elsevier B.V., All rights reserved.