scholarly journals Tyrosine kinase inhibitors impair B-cell immune responses in CML through off-target inhibition of kinases important for cell signaling

Blood ◽  
2013 ◽  
Vol 122 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Hugues de Lavallade ◽  
Ahmad Khoder ◽  
Melanie Hart ◽  
Anushruti Sarvaria ◽  
Takuya Sekine ◽  
...  

Key Points TKIs impair B-cell immune responses in CML through off-target inhibition of kinases important for B-cell signaling. Our results call for close monitoring of patients on TKI to assess the long-term impact of impaired B-cell function.

2019 ◽  
Vol 3 (12) ◽  
pp. 1891-1896 ◽  
Author(s):  
Elisavet Chartomatsidou ◽  
Stavroula Ntoufa ◽  
Konstantia Kotta ◽  
Alessandra Rovida ◽  
Maria Anna Akritidou ◽  
...  

Key Points Microenvironmental stimuli affect EZH2 expression and function in CLL. Combined B-cell signaling and EZH2 inhibition showed synergistic effects on primary CLL cells.


2016 ◽  
Vol 94 (9) ◽  
pp. 830-837 ◽  
Author(s):  
Nadine Voelxen ◽  
Claudia Wehr ◽  
Sylvia Gutenberger ◽  
Baerbel Keller ◽  
Miriam Erlacher ◽  
...  

Immunity ◽  
2010 ◽  
Vol 33 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Elissa K. Deenick ◽  
Anna Chan ◽  
Cindy S. Ma ◽  
Dominique Gatto ◽  
Pamela L. Schwartzberg ◽  
...  

2021 ◽  
Author(s):  
Yuezhou Chen ◽  
Pei Tong ◽  
Noah B. Whiteman ◽  
Ali Sanjari Moghaddam ◽  
Adam Zuiani ◽  
...  

ABSTRACTOptimal immune responses furnish long-lasting (durable) antibodies protective across dynamically mutating viral variants (broad). To assess robustness of mRNA vaccine-induced immunity, we compared antibody durability and breadth after SARS-CoV-2 infection and vaccination. While vaccination delivered robust initial virus-specific antibodies with some cross-variant coverage, pre-variant SARS-CoV-2 infection-induced antibodies, while modest in magnitude, showed highly stable long-term antibody dynamics. Vaccination after infection induced maximal antibody magnitudes with enhanced longitudinal stability while infection-naïve vaccinee antibodies fell with time to post-infection-alone levels. The composition of antibody neutralizing activity to variant relative to original virus also differed between groups, with infection-induced antibodies demonstrating greater relative breadth. Differential antibody durability trajectories favored COVID-19-recovered subjects with dual memory B cell features of greater early antibody somatic mutation and cross-coronavirus reactivity. By illuminating an infection-mediated antibody breadth advantage and an anti-SARS-CoV-2 antibody durability-enhancing function conferred by recalled immunity, these findings may serve as guides for ongoing vaccine strategy improvement.


Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 237-242
Author(s):  
Jorge Cortes

Abstract Patients with chronic myeloid leukemia (CML) often have comorbidities, at an incidence that might be higher than in the general population. Because of the favorable outcome of most patients with CML treated with tyrosine kinase inhibitors (TKIs), a greater number of comorbidities might be the most significant adverse feature for long-term survival. The presence of comorbidities may also affect the risk of developing adverse events with TKIs. This effect is perhaps best exemplified by the risk of developing arterio-occlusive events, which is greatest for patients who have other risk factors for such events, with the risk increasing with higher numbers of comorbidities. The coexistence of comorbidities in patients with CML not only may affect TKI selection but also demands close monitoring of the overall health condition of the patient to optimize safety and provide the opportunity for an optimal outcome to such patients. With optimal, holistic management of leukemia and all other conditions afflicting them, patients with CML and comorbidities may aim for a near-normal life expectancy, just as the more select patients enrolled in clinical trials now enjoy.


2010 ◽  
Vol 107 (29) ◽  
pp. 12747-12754 ◽  
Author(s):  
J. M. Irish ◽  
J. H. Myklebust ◽  
A. A. Alizadeh ◽  
R. Houot ◽  
J. P. Sharman ◽  
...  

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