Acute Myeloid Leukemia Mutations and Future Mechanistic Target to Overcome Resistance

Curr Treat Options Oncol. 2021 Jul 2;22(9):76. doi: 10.1007/s11864-021-00880-x.

Abstract

Cytogenetics and mutation identification in acute myeloid leukemia have allowed for more targeted therapy. Many therapies have been approved by the FDA in the last 3 years including gilteritinib and azacitidine but the overall survival has remained stagnant at 25%. The inability to achieve complete remission was related to the residual leukemic stem cells (LSCs). Thus, the relationship between bone marrow niche and LSCs must be further explored to prevent treatment relapse/resistance. The development of immunotherapy and nanotechnology may play a role in future therapy to achieve the complete remission. Nano-encapsulation of drugs can improve drugs' bioavailability, help drugs evade resistance, and provide combination therapy directly to the cancer cells. Studies indicate targeting surface antigens such as CLL1 and CD123 using chimeric antibody receptor T cells can improve survival outcomes. Finally, new discoveries indicate that inhibiting integrin αvβ3 and acid ceramidase may prove to be efficacious.

Keywords: Acid ceramidase; Acute myeloid leukemia resistance; BCL-2; Bone marrow microenvironment; CAR T; FLT3; Hedgehog; Immunotherapy; Nanotechnology.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • Combined Modality Therapy / methods
  • Disease Susceptibility
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy*
  • Molecular Targeted Therapy* / adverse effects
  • Molecular Targeted Therapy* / methods
  • Mutation*
  • Nanomedicine
  • Precision Medicine
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor