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A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia
Publication . Vinhas, Raquel; Lourenço, Alexandra; Santos, Susana; Lemos, Marcos; Ribeiro, Patrícia; de Sousa, Aida Botelho; Baptista, Pedro Viana; Fernandes, Alexandra Ramos; UCIBIO - Applied Molecular Biosciences Unit; DCV - Departamento de Ciências da Vida; Dove Medical Press
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%–30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient’s resistance and disease relapse. Here, we report a Ph+ B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190BCR-ABL1 isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.
Multifunctional microfluidic chip for optical nanoprobe based RNA detection - Application to Chronic Myeloid Leukemia
Publication . Alves, Pedro Urbano; Vinhas, Raquel; Fernandes, Alexandra R.; Birol, Semra Zuhal; Trabzon, Levent; Bernacka-Wojcik, Iwona; Igreja, Rui; Lopes, Paulo; Baptista, Pedro Viana; Águas, Hugo; Fortunato, Elvira; Martins, Rodrigo; UCIBIO - Applied Molecular Biosciences Unit; DCV - Departamento de Ciências da Vida; CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; Nature Publishing Group
Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.
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Fundação para a Ciência e a Tecnologia
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PD
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PD/BD/52211/2013