New Therapeutic Strategies for Adult Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis and prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies and allogeneic transplantation, and a variety of new agents and treatment strategies have emerged. After over 20 years during which no new drugs became available for the treatment of AML, the CD33-targeting antibody–drug conjugate gemtuzumab ozogamicin was developed. This is currently used in combination with standard chemotherapy or as a single agent. CPX-351, a liposomal formulation containing daunorubicin and cytarabine, has become one of the standard treatments for secondary AML in the elderly. FMS-like tyrosine kinase 3 (FLT3) inhibitors and isocitrate dehydrogenase 1/2 (IDH 1/2) inhibitors are mainly used for AML patients with actionable mutations. In addition to hypomethylating agents and venetoclax, a B-cell lymphoma-2 inhibitor is used in frail patients with newly diagnosed AML. Recently, tumor protein p53 inhibitors, cyclin-dependent kinase inhibitors, and NEDD8 E1-activating enzyme inhibitors have been gaining attention, and a suitable strategy for the use of these drugs is required. Antibody drugs targeting cell-surface markers and immunotherapies, such as antibody–drug conjugates and chimeric antigen receptor T-cell therapy, have also been developed for AML.

Robust Harmonization of Microbiome Studies by Phylogenetic Scaffolding with MaLiAmPi

“…Revisiting prior ‘omics studies has proven a fruitful way to improve patient care. For example, it is now common practice to use genomics data to personalize and optimize cancer treatment regimens, significantly improving outcomes for patients 27,28 . Similarly, transcriptional 29 and epigenomics studies are being combined and revisited with newer machine-learning techniques with an eye towards drug repurposing and personalized medicine.…”

A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia

“…The European LeukemiaNet (ELN) risk stratification and the National Comprehensive Cancer Network (NCCN) guidelines classify AML patients into three groups that are associated with specific prognoses and may guide medical decision-making: favorable, intermediate, and poor (16). The classification is based on chromosomal and genetic abnormalities that certainly may have therapeutic significance, and likely to be changed as newer strategies become available.…”

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

“…Compared with ubiquitination, sumoylation of p53 does not promote the degradation of p53 but inhibits the transcriptional activation of p53 on target genes by competing with acetyl for lysine residues in CTR 113 . NEDD8 is a ubiquitin‐like small molecule with a high similarity to ubiquitin 114 . NEDDylation can not only directly inhibit the transcriptional activity of p53, but also prevent the degradation of MDM2, and indirectly promote the ubiquitination of p53 by MDM2 18 …”