Targeting Tyrosine Kinases in Acute Myeloid Leukemia: Why, Who and How?

• Published in: International journal of molecular sciences 2019-07, Vol.20 (14), p.3429
• Main Authors: Fernandez, Solène, Desplat, Vanessa, Villacreces, Arnaud, Guitart, Amélie V, Milpied, Noël, Pigneux, Arnaud, Vigon, Isabelle, Pasquet, Jean-Max, Dumas, Pierre-Yves
• Format: Article
• Language: English
• Subjects: Abnormalities; Acute myeloid leukemia; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biochemistry, Molecular Biology; Biological activity; Biomarkers, Tumor; Blood; Blood cells; Bone marrow; c-Kit protein; Cancer; Chromatin; Clinical trials; Clinical Trials as Topic; Cohesin; Deoxyribonucleic acid; Deregulation; DNA; DNA methylation; Epigenetics; Gene Expression Regulation, Leukemic; Genes; Growth factors; Hematology; Hematopoiesis; Hematopoietic stem cells; Human health and pathology; Humans; inhibitors; Kinases; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Life Sciences; Ligands; Medical prognosis; Molecular Targeted Therapy; Mutation; Myeloid leukemia; p53 Protein; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; Proteome; PTEN protein; Review; Runx1 protein; Signal Transduction; Stem cells; targeted therapy; Transcription factors; Transcriptome; Treatment Outcome; Tumor suppressor genes; Tyrosine; tyrosine kinase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20143429

Acute myeloid leukemia (AML) is a myeloid malignancy carrying a heterogeneous molecular panel of mutations participating in the blockade of differentiation and the increased proliferation of myeloid hematopoietic stem and progenitor cells. The historical "3 + 7" treatment (cytarabine and daunorubicin) is currently challenged by new therapeutic strategies, including drugs depending on the molecular landscape of AML. This panel of mutations makes it possible to combine some of these new treatments with conventional chemotherapy. For example, the FLT3 receptor is overexpressed or mutated in 80% or 30% of AML, respectively. Such anomalies have led to the development of targeted therapies using tyrosine kinase inhibitors (TKIs). In this review, we document the history of TKI targeting, FLT3 and several other tyrosine kinases involved in dysregulated signaling pathways.