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1.	Wästerlid, Tove, et al. (författare) Application of precision medicine in clinical routine in haematology-Challenges and opportunities 2022 Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 292:2, s. 243-261 Forskningsöversikt (refereegranskat)abstract Precision medicine is revolutionising patient care in cancer. As more knowledge is gained about the impact of specific genetic lesions on diagnosis, prognosis and treatment response, diagnostic precision and the possibility for optimal individual treatment choice have improved. Identification of hallmark genetic aberrations such as the BCR::ABL1 gene fusion in chronic myeloid leukaemia (CML) led to the rapid development of efficient targeted therapy and molecular follow-up, vastly improving survival for patients with CML during recent decades. The assessment of translocations, copy number changes and point mutations are crucial for the diagnosis and risk stratification of acute myeloid leukaemia and myelodysplastic syndromes. Still, the often heterogeneous and complex genetic landscape of haematological malignancies presents several challenges for the implementation of precision medicine to guide diagnosis, prognosis and treatment choice. This review provides an introduction and overview of the important molecular characteristics and methods currently applied in clinical practice to guide clinical decision making in haematological malignancies of myeloid and lymphoid origin. Further, experimental ways to guide the choice of targeted therapy for refractory patients are reviewed, such as functional precision medicine using drug profiling. An example of the use of pipeline studies where the treatment is chosen according to the molecular characteristics in rare solid malignancies is also provided. Finally, the future opportunities and remaining challenges of precision medicine in the real world are discussed.
2.	Zabriskie, Matthew S., et al. (författare) BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia 2014 Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442 Tidskriftsartikel (refereegranskat)abstract Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.

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Resultat 1-2 av 2

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Typ av publikation: tidskriftsartikel (1); forskningsöversikt (1)

Typ av innehåll: refereegranskat (2)

Författare/redaktör: Konopleva, Marina (2); Smedby, Karin E. (1); Cavelier, Lucia (1); Fioretos, Thoas (1); Friedman, Ran (1); Hernandez-Boluda, Ju ... (1); visa fler...; Barbany, Gisela (1); Baccarani, Michele (1); Rosti, Gianantonio (1); Kantarjian, Hagop (1); Deininger, Michael W ... (1); Soverini, Simona (1); Cortes, Jorge E. (1); Larson, Richard A. (1); Lipton, Jeffrey H. (1); Mahon, Francois-Xavi ... (1); Rousselot, Philippe (1); Haferlach, Claudia (1); Ossenkoppele, Gert J (1); O'Hare, Thomas (1); Stenke, Leif (1); Druker, Brian J. (1); Etienne, Gabriel (1); Bullinger, Lars (1); Wästerlid, Tove (1); Goldberg, Stuart L. (1); Froehling, Stefan (1); Khoury, Hanna J (1); Ostling, Päivi (1); Press, Richard D. (1); Zabriskie, Matthew S ... (1); Eide, Christopher A. (1); Tantravahi, Srinivas ... (1); Vellore, Nadeem A. (1); Estrada, Johanna (1); Nicolini, Franck E. (1); Jabbour, Elias J. (1); Kornblau, Steven M. (1); Rea, Delphine (1); Lange, Thoralf (1); Chuah, Charles (1); Wetzler, Meir (1); Deininger, Marie (1); Reynolds, Kimberly R ... (1); Heaton, William L. (1); Eiring, Anna M. (1); Pomicter, Anthony D. (1); Khorashad, Jamshid S ... (1); Kelley, Todd W. (1); Baron, Riccardo (1); visa färre...

Lärosäte: Karolinska Institutet (2); Uppsala universitet (1); Lunds universitet (1); Linnéuniversitetet (1)

Språk: Engelska (2)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (2)

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