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Clinical-genomic profiling of MDS to inform allo-HCT: recommendations from an i...

Gurnari, Carmelo; Robin, Marie; Adès, Lionel; Aljurf, Mahmoud; Almeida, António M.; Duarte, Fernando Barroso; Bernard, Elsa; Cutler, Corey

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes co...


Genetic variants in oxidative stress-related genes and their impact on prognosi...

Alves, Raquel; Ventura, Filipa; Jorge, Joana; Marques, Gilberto; Coucelo, Margarida; Diamond, Joana; Oliveiros, Bárbara; Pereira, Amélia

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR::ABL1 fusion gene, which codifies the BCR-ABL protein with increased tyrosine kinase activity. Despite the clinical results for the outstanding tyrosine kinase inhibitors (TKIs), drug resistance is a problem in CML management. Genetic variants that alter redox homeostasis by changing antioxidant enzyme expression or...


Combination of elacridar with imatinib modulates resistance associated with dru...

Alves, Raquel; Gonçalves, Ana Cristina; Jorge, Joana; Almeida, António M.; Sarmento-Ribeiro, Ana Bela

Multidrug resistance (MDR) development has emerged as a complication that compromises the success of several chemotherapeutic agents. In chronic myeloid leukemia (CML), imatinib resistance has been associated with changes in BCR-ABL1 and intracellular drug concentration, controlled by SLC and ABC transporters. We evaluate the therapeutic potential of a P-glycoprotein and BCRP inhibitor, elacridar, in sensitive ...


Genetic variants of ABC and SLC transporter genes and chronic myeloid leukaemia...

Alves, Raquel; Goncalves, Ana Cristina; Jorge, Joana; Marques, Gilberto; Ribeiro, André B.; Tenreiro, Rita; Coucelo, Margarida; Diamond, Joana

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially pre...


Resistance to tyrosine kinase inhibitors in chronic myeloid leukemia — from mol...

Alves, Raquel; Gonçalves, Ana Cristina; Rutella, Sergio; Almeida, António M.; Rivas, Javier De Las; Trougakos, Ioannis P.; Ribeiro, Ana Bela Sarmento

Resistance to targeted therapies is a complex and multifactorial process that culminates in the selection of a cancer clone with the ability to evade treatment. Chronic myeloid leukemia (CML) was the first malignancy recognized to be associated with a genetic alteration, the t(9;22)(q34;q11). This translocation originates the BCR-ABL1 fusion gene, encoding the cytoplasmic chimeric BCR-ABL1 protein that displays...


MicroRNA signature refine response prediction in CML

Alves, Raquel; Gonçalves, Ana Cristina; Jorge, Joana; Marques, Gilberto João Padilha; Luís, Dino; Ribeiro, André B.; Tavares, Paulo; Oliveiros, Bárbara

microRNAs (miRs) dysregulation have emerged as a crucial step in tumorigenesis, being related with cancer development, progression and response to treatment. In chronic myeloid leukaemia (CML), the resistance to tyrosine kinase inhibitors (TKI) is responsible for treatment failure and could be linked to changes in miRs expression. This work aimed to correlate the expression levels of 3 miRs, miR-21, miR-26b and...


MicroRNA signature refine response prediction in CML

Alves, Raquel; Gonçalves, Ana Cristina; Jorge, Joana; Marques, Gilberto; Luís, Dino; Ribeiro, André B.; Freitas-Tavares, Paulo; Oliveiros, Bárbara

microRNAs (miRs) dysregulation have emerged as a crucial step in tumorigenesis, being related with cancer development, progression and response to treatment. In chronic myeloid leukaemia (CML), the resistance to tyrosine kinase inhibitors (TKI) is responsible for treatment failure and could be linked to changes in miRs expression. This work aimed to correlate the expression levels of 3 miRs, miR-21, miR-26b and...


MORPhA Scale: behavioral and electroencephalographic validation of a rodent ane...

Esteves, Madalena; Almeida, António M.; Silva, Joana Margarida Gonçalves Mota; Moreira, Pedro Miguel Silva; Carvalho, Emanuel; Pêgo, José M.

Background: Laboratory practice commonly implies rodent anesthesia. Such is instrumental not only for animal welfare, but also for standardized assessment of new anesthetics. New method: We developed and validated a grading system for a temporal follow-up of anesthesia. The Minho Objective Rodent Phenotypical Anesthesia (MORPhA) scale was tested in mice (C57BL/6 J) and rats (WistarHan) anesthetized with ketamin...



The bone marrow-mediated protection of myeloproliferative neoplastic cells to V...

Cardoso, Bruno A.; Belo, Hélio; Barata, João T.; Almeida, António M.

The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN) are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi), albeit with poorer toler...


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