26 research outputs found
The differences in thermal profiles between normal and leukemic cells exposed to anticancer drug evaluated by differential scanning calorimetry
Chronic lymphocytic leukemia (CLL) is a heterogenous disease with an imbalance between apoptosis and cell proliferation. Therefore, the main goal in CLL therapy is to induce apoptosis and effectively support this process in transformed B lymphocytes. In the current study, we have compared differential scanning calorimetry (DSC) profiles of nuclei isolated from CLL cells and normal mononuclear cells exposed to cladribine or fludarabine combined with mafosfamide (CM; FM), and additionally to CM combined with monoclonal antibody—rituximab (RCM) for 48 h, as well as in culture medium only (controls). Under current study, the mononuclear cells from peripheral blood (PBMCs) of healthy individuals have been included. The obtained results have shown the presence of thermal transition at 95 ± 5 °C in most of nuclear preparations (92.2 %) isolated from blood of CLL patients. This thermal characteristic parameter was changed after drug exposure, however, to a different extent. These thermal changes were accompanied by the decrease of cell viability, an elevation of apoptosis rate and the changes in expression/proteolysis of poly(ADP-ribose)polymerase-1—main marker of apoptosis. Importantly, in DSC profiles of nuclear preparations of PBMCs from blood of healthy donors exposed to investigated drug combinations and control CLL cells, the lack of such changes was observed. Our results confirmed that DSC technique complemented with other biological approaches could be helpful in tailoring therapy for CLL patients.Research was sponsored by Grant from the
Polish National Science Centre (No. 2011/01/B/NZ/0102); Results of
presented study were partially presented in oral presentation on 2nd
Central and Eastern European Conference on Thermal Analysis and
Calorimetry in Vilnius, Lithuania, 201
Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma
Bruton tyrosine kinase (BTK) inhibitors have greatly
improved the spectrum of treatment options in mantle cell
lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective,
orally administered, and potent BTK inhibitor with limited
off-target activity [5]. Acalabrutinib was approved in 2017
by the US Food and Drug Administration for the treatment
of relapsed/refractory MCL based on clinical data from the
open-label, multicenter, phase 2 ACE-LY-004 study of
acalabrutinib 100 mg twice daily [1]. Here, we present
updated results from the ACE-LY-004 study after a median
26-month follow-up.
Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal
residual disease (MRD) was conducted after complete
response (CR) or partial response (PR) was achieved
using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6
) assay (Adpative Biotechnologies, Seattle,
WA, USA) in consenting patients with available paired
archival tumor and whole blood samples. Data are updated
as of February 12, 2018