Ibrutinib, an inhibitor of Bruton’s tyrosine kinase, and venetoclax, an inhibitor of B-cell lymphoma 2 protein, have been approved for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations have indicated potential synergistic interaction of their combination.

In 1957, Hillestad et al. defined acute promyelocytic leukemia (APL) for the first time in the literature as a distinct type of acute myeloid leukemia (AML) with a “rapid downhill course” characterized with a severe bleeding tendency. APL, accounting for 10–15% of the newly diagnosed AML cases, results from a balanced translocation, t(15;17) (q22;q12-21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. The PML–RARA fusion oncoprotein induces leukemia by blocking normal myeloid differentiation. Before using anthracyclines in APL therapy in 1973, no effective treatment was available. In the mid-1980s, all-trans retinoic acid (ATRA) monotherapy was used with high response rates, but response durations were short. Later, the development of ATRA, chemotherapy, and arsenic trioxide combinations turned APL into a highly curable malignancy. In this review, we summarize the evolution of APL therapy, focusing on key milestones that led to the standard-of-care APL therapy available today and discuss treatment algorithms and management tips to minimize induction mortality.

The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.