Granty a projekty

Hodnotenie ABC transportérov v akútnej myeloidnej leukémii a ich interakcie s novými FLT3 inhibítormi ako potenciálne sľubná terapeutická stratégia

Acute myeloid leukemia (AML) remains rapidly progressing hematological malignancy hard to defeat in multiple cases. Pharmacotherapy of AML is often compromised by the development of a resistant immunophenotype associated with overexpression of ABC efflux transporters. The chemoresistance is preserved within leukemia stem cells (LSCs) found mainly in CD34+/CD38- subpopulation, but developing also from precursor GM-like CD34- AML cells. Here we aim to evaluate ABC transporters expressed in their dominant cellular subpopulations with respect to AML diagnostic markers. The novel FLT3 inhibitors will be subsequently tested for their ability to inhibit ABC transporters and potentiate the effect of chemotherapeutics in resistant cells. A combination of experimental methods will be employed, including in vitro accumulation and apoptosis assays in HL60 cell line and the resistant variants as well as ex vivo apoptosis and digital droplet PCR (ddPCR) gene expression studies on leukemic cells isolated from peripheral blood and bone marrow of patients de novo diagnosed for AML and those in remission and relapse stage of the disease. Cell sorting will be applied to select particular subpopulations and address LSCs’ characteristics. The outcomes of this project aim to broaden current knowledge on the role of ABC transporters in AML, helping to stratify AML patients in order to individualize pharmacotherapy and thereby improve the efficiency of the treatment.

Číslo: GAUK1358120

Období: 01.01.2020 - 31.12.2022

Poskytovatel: Univerzita Karlova - Grantová agentura UK

Hlavní řešitel: Suchá Simona PharmDr., Ph.D. - Farmaceutická fakulta v Hradci Králové

Celkový objem financí: 870 000,00 Kč

Interní řešitelé

Hlavní řešitel: PharmDr. Simona Suchá, Ph.D. - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Simona Dudičová - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Martin Huličiak - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Fahda Ahmed - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Aleš Šorf, Ph.D. - Univerzita Karlova,
Školitel: doc. PharmDr. Martina Čečková, Ph.D. - Univerzita Karlova,