B-cell chronic lymphocytic leukemia-associated nuclear antigens

One- and two-dimensional polyacrylamide gel electrophoresis were used to compare the composition of nuclear polypeptides from normal and В-cell chronic lymphocytic leukemia mononuclear cells. Against two electrophoretically-specific nuclear proteins with molecular weight of 38/39 and 44/46 kD a from leukemic cells rabbit sera were obtained. As it was analyzed by Western blot technique the available antisera recognized the 38/39 kDa antigen in 53 of the 56 (94.6%), while the 44/46 kDa in 46 of the 49 (93.9%) of examined В-CLL nuclear fraction preparations, but not in normal ones. The pi values of described leukaemia-specific antigens were determined; p38/39 had pi in the range of pH 6.55 -7.00 and p44/46 - in the range of pH 6.2-6.4.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

Towards the Application of Atorvastatin to Intensify Proapoptotic Potential of Conventional Antileukemic Agents In Vitro

It has been previously revealed that statins used at high concentrations display antileukemic potential towards chronic lymphocytic leukemia (CLL) cells. However, their usage alone in clinical practice may be limited due to possible side effects of high doses of these drugs. On the other hand, combined treatment of leukemia with statins and the conventional chemotherapeutics is questionable because of unknown influence of the first on the standard treatment results. This study has revealed that in vitro atorvastatin increases the proapoptotic potential of cladribine and mafosfamide in CLL cells isolated from peripheral blood of patients. Moreover, a preincubation with the above statin sensitizes leukemic cells to CM-induced apoptosis even at small concentrations of the drug. The usage of atorvastatin together with or followed by the conventional chemotherapy should be considered as therapeutic option for the treatment for this leukemia. Interestingly, CM-resistant patients might have the biggest benefits from atorvastatin administration.Grant no. 1407 from the University of Łódź

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