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Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy

  • Leukemia (PH Wiernik, Section Editor)
  • Published:
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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.

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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

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Correspondence to Shaker A. Mousa PhD.

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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.

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Sami, S.A., Darwish, N.H.E., Barile, A.N.M. et al. Current and Future Molecular Targets for Acute Myeloid Leukemia Therapy. Curr. Treat. Options in Oncol. 21, 3 (2020). https://doi.org/10.1007/s11864-019-0694-6

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