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Autor
Allen, Steven L 1 Barrientos, Jacqueline C 1 Belessi, Chrysoula 1 Brown, Jennifer R 1 Byrd, John C 1 Catherwood, Mark 1 Chiorazzi, Nicholas 1 Davi, Frederic 1 Davis, Zadie 1 Ghia, Emanuela M 1 Ghia, Paolo 1 Kaufman, Matthew 1 Kay, Neil E 1 Kipps, Thomas J 1 Kolitz, Jonathan E 1 Langerak, A. W 1 Li, Wentian 1 Montillo, Marco 1 Neuberg, Donna 1 Oscier, David 1
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Pracoviště
Center for Novel Therapeutics Moores ... 1 Chronic Lymphocytic Leukemia Center D... 1 Clinical Hematology Belfast City Hosp... 1 Department of Biological Hematology H... 1 Department of Data Science Dana Farbe... 1 Department of Hematology Royal Bourne... 1 Department of Hematology and Oncology... 1 Department of Internal Medicine Hemat... 1 Department of Internal Medicine Unive... 1 Department of Molecular Medicine Dona... 1 Department of Molecular Medicine and ... 1 Department of Molecular Pathology Roy... 1 Departments of Medicine Donald and Ba... 1 Division of Experimental Oncology IRC... 1 Division of Hematology Mayo Clinic Ro... 1 Hematology Department Nikea General H... 1 Hematology Unit Department of Medicin... 1 Institute of Applied Biosciences Cent... 1 Karches Center for Oncology Research ... 1 Laboratory Medical Immunology Departm... 1
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Autor
Allen, Steven L 1 Barrientos, Jacqueline C 1 Belessi, Chrysoula 1 Brown, Jennifer R 1 Byrd, John C 1 Catherwood, Mark 1 Chiorazzi, Nicholas 1 Davi, Frederic 1 Davis, Zadie 1 Ghia, Emanuela M 1 Ghia, Paolo 1 Kaufman, Matthew 1 Kay, Neil E 1 Kipps, Thomas J 1 Kolitz, Jonathan E 1 Langerak, A. W 1 Li, Wentian 1 Montillo, Marco 1 Neuberg, Donna 1 Oscier, David 1
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Pracoviště
Center for Novel Therapeutics Moores ... 1 Chronic Lymphocytic Leukemia Center D... 1 Clinical Hematology Belfast City Hosp... 1 Department of Biological Hematology H... 1 Department of Data Science Dana Farbe... 1 Department of Hematology Royal Bourne... 1 Department of Hematology and Oncology... 1 Department of Internal Medicine Hemat... 1 Department of Internal Medicine Unive... 1 Department of Molecular Medicine Dona... 1 Department of Molecular Medicine and ... 1 Department of Molecular Pathology Roy... 1 Departments of Medicine Donald and Ba... 1 Division of Experimental Oncology IRC... 1 Division of Hematology Mayo Clinic Ro... 1 Hematology Department Nikea General H... 1 Hematology Unit Department of Medicin... 1 Institute of Applied Biosciences Cent... 1 Karches Center for Oncology Research ... 1 Laboratory Medical Immunology Departm... 1
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Free Medical Journals od 2011
PubMed Central od 2011
Europe PubMed Central od 2011
Open Access Digital Library od 2011-01-01
Open Access Digital Library od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources od 2011
PubMed
35903706
DOI
10.3389/fonc.2022.897280
Knihovny.cz E-zdroje
Patients with CLL with mutated IGHV genes (M-CLL) have better outcomes than patients with unmutated IGHVs (U-CLL). Since U-CLL usually express immunoglobulins (IGs) that are more autoreactive and more effectively transduce signals to leukemic B cells, B-cell receptor (BCR) signaling is likely at the heart of the worse outcomes of CLL cases without/few IGHV mutations. A corollary of this conclusion is that M-CLL follow less aggressive clinical courses because somatic IGHV mutations have altered BCR structures and no longer bind stimulatory (auto)antigens and so cannot deliver trophic signals to leukemic B cells. However, the latter assumption has not been confirmed in a large patient cohort. We tried to address the latter by measuring the relative numbers of replacement (R) mutations that lead to non-conservative amino acid changes (Rnc) to the combined numbers of conservative (Rc) and silent (S) amino acid R mutations that likely do not or cannot change amino acids, "(S+Rc) to Rnc IGHV mutation ratio". When comparing time-to-first-treatment (TTFT) of patients with (S+Rc)/Rnc ≤ 1 and >1, TTFTs were similar, even after matching groups for equal numbers of samples and identical numbers of mutations per sample. Thus, BCR structural change might not be the main reason for better outcomes for M-CLL. Since the total number of IGHV mutations associated better with longer TTFT, better clinical courses appear due to the biologic state of a B cell having undergone many stimulatory events leading to IGHV mutations. Analyses of larger patient cohorts will be needed to definitively answer this question.
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Po ukončení testovacího provozu bude odkaz přesměrován adresu produkční verze portálu Medvik.