A5044287102- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Phagocytosis and Immune Regulation
- Advanced Breast Cancer Therapies
- Cancer-related gene regulation
- Antiplatelet Therapy and Cardiovascular Diseases
- CAR-T cell therapy research
- Synthesis and Catalytic Reactions
- RNA Research and Splicing
National Institutes of Health
2022-2024
National Heart Lung and Blood Institute
2022-2024
To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL).In treated acalabrutinib (n=48), expression, VLA-4 integrin activation, and tumor transcriptomes CLL cells were assessed. Clinical responses BTKis investigated (n=48; NCT02337829), ibrutinib (n=73; NCT01500733) patients.In acalabrutinib, treatment induced lymphocytosis was comparable both subgroups but resolved more rapidly CD49d+ cases. Acalabrutinib...
Abstract Progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) on ibrutinib often presents acquired mutations BTK and/or PLCG2. Reported variant allele frequencies (VAF) are low, leading some to question the role of these mutations. Further, several co-existing identified. Here we investigated clonal composition PD single cell level, across time, and different anatomic compartments. 84 CLL (52 treatment-naïve; 32 relapsed/refractory) either a TP53 aberration or age ≥65...
<div>Abstract<p>Purpose: To determine the role of CD49d for response to Bruton’s tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). Methods: In treated acalabrutinib (n=48), expression, VLA-4 integrin activation, and tumor transcriptomes CLL cells were assessed. Clinical responses BTKis investigated (n=48; NCT02337829), ibrutinib (n=73; NCT01500733) patients. Results: acalabrutinib, treatment induced lymphocytosis was comparable both subgroups...
<p>Supplementary Figure S3. In vivo effect of acalabrutinib on the VLA-4 activation upon BCR and chemokine signaling</p>
<p>Supplementary Figure S5. Time to disease progression, prevalence of resistance mutations, and risk category by CLL-4 model</p>
<p>Supplementary Figure S3. In vivo effect of acalabrutinib on the VLA-4 activation upon BCR and chemokine signaling</p>
<p>Supplementary Figure S5. Time to disease progression, prevalence of resistance mutations, and risk category by CLL-4 model</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S4. Clinical impact of CD49d bimodal expression on durability BTKi therapy.</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S4. Clinical impact of CD49d bimodal expression on durability BTKi therapy.</p>
<p>Supplementary Figure S1. Tumor volume in CD49d+ and CD49d− CLL during acalabrutinib treatment</p>
<p>Supplementary Figure S2. In vivo effect of acalabrutinib on the expression CD49d</p>
<p>Supplementary Figure S2. In vivo effect of acalabrutinib on the expression CD49d</p>