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Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy

  • Shaheedul A. Sami
  • Noureldien H. E. Darwish
  • Amanda N. M. Barile
  • Shaker A. MousaEmail author
Leukemia (PH Wiernik, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Leukemia

Opinion statement

Acute myeloid leukemia (AML) disease prognosis is poor and there is a high risk of chemo-resistant relapse for both young and old patients. Thus, there is a demand for alternative and target-specific drugs to improve the 5-year survival rate. Current treatment mainstays include chemotherapy, or mutation-specific targeting molecules including FLT3 inhibitors, IDH inhibitors, and monoclonal antibodies. Efforts to devise new, targeted therapy have included recent advances in methods for high-throughput genomic screening and the availability of computer-assisted techniques for the design of novel agents predicted to specifically inhibit mutant molecules involved in leukemogenesis. Crosstalk between the leukemia cells and the bone marrow microenvironment through cell surface molecules, such as the integrins αvβ3 and αvβ5, might influence drug response and AML progression. This review article focuses on current AML treatment options, new AML targeted therapies, the role of integrins in AML progression, and a potential therapeutic agent—integrin αvβ3 antagonist.

Keywords

B-cell lymphoma gene 2 FMS-like tyrosine kinase 3 Isocitrate dehydrogenase Nano-diamino-tetrac l-Thyroxine tetraiodothyroacetic acid 

Abbreviations

AML

Acute myeloid leukemia

BCL-2

B-cell lymphoma gene 2

CAM

Chick egg chorioallantoic membrane

CDK

Cyclin-dependent kinase

c-KIT

C-kit is a type of receptor tyrosine kinase, also called CD117

c-FMS

Proto-oncogene that codes for the MCSF (CSF1) receptor

EGF

Epidermal growth factor

EGFR

EGF receptor

EMT

Epithelial–mesenchymal transition

FAK

Focal adhesion kinase

FGF

Basic fibroblast growth factor

FLT3

FMS-like tyrosine kinase 3

IDH

Isocitrate dehydrogenase

JAK-2

Janus kinase-2

LSD

Lysine-specific demethylase

MAPK

Mitogen-activated protein kinase

MDM2

Mouse double minute chromosome 2

miR

MicroRNAs

NDAT

Nano-diamino-tetrac

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NPM

Nucleophosmin

P-bi-TAT

Polyethylene glycol (PEG) covalently bonded with two bi-tri-azole tetraiodothyroacetic acid molecules

PD-1

Programmed cell death protein 1

PD-L1

Programmed death-ligand 1

PDGF

Platelet-derived growth factor

PEG

Polyethylene glycol

PI3K

Phosphatidylinositol 3-kinase

STAT

Signal transducer and activator of transcription

Tetrac

Tetraiodothyroacetic acid

TGFβ

Transforming growth factor β

TK

Tyrosine kinase

T4

l-Thyroxine

Notes

Funding

There is no funding to report.

Compliance with Ethical Standards

Conflict of Interest

Shaheedul A. Sami declares that he has no conflict of interest.

Noureldien H. E. Darwish declares that he has no conflict of interest.

Amanda N. M. Barile declares that she has no conflict of interest.

Shaker A. Mousa was issued a patent that is owned by NanoPharmaceuticals LLC, and he owns stock in NanoPharmaceuticals LLC, which is developing anticancer drugs.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Pharmaceutical Research InstituteAlbany College of Pharmacy and Health SciencesRensselaerUSA
  2. 2.Hematology Unit, Clinical Pathology Department, Mansoura Faculty of MedicineMansoura UniversityMansouraEgypt

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