title: Receptor Tyrosine Kinases: Translocation Partners in Hematopoietic Disorders.
abstract: Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation. While RTK translocations in hematological malignancies are relatively rare, clinical evidence suggests that patients with these genetic abnormalities benefit from RTK-targeted inhibitors. Here, we present a timely review of an exciting field by examining RTK chromosomal translocations in hematological cancers, such as Anaplastic Lymphoma Kinase (ALK), Fibroblast Growth Factor Receptor (FGFR), Platelet-Derived Growth Factor Receptor (PDGFR), REarranged during Transfection (RET), Colony Stimulating Factor 1 Receptor (CSF1R), and Neurotrophic Tyrosine Kinase Receptor Type 3 (NTRK3) fusions, and discuss current therapeutic options.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Katelyn N
authors.initials: KN
authors.lastname: Nelson
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Malalage N
authors.initials: MN
authors.lastname: Peiris
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: April N
authors.initials: AN
authors.lastname: Meyer
authors.affiliation: Université Joseph Fourier Grenoble, Grenoble, France.
authors.forename: Asma
authors.initials: A
authors.lastname: Siari
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA; Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: ddonoghue@ucsd.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Donoghue
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014178:Translocation, Genetic
chemical_list: D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D017468:Receptors, Fibroblast Growth Factor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor
keywords: ALK; FGFR; PDGFR.; leukemia; lymphoma; oncogenic fusion