Katarzyna Skorka

Expression of Programmed Death 1 Ligand in Different Compartments of Chronic Lymphocytic Leukemia.

Background: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. Methods: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. Results: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PD-L1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. Conclusion: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.

The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia

Programmed death-1 (PD-1) is a negative receptor expressed on lymphocytes including malignant B cells in chronic lymphocytic leukemia (CLL). In this work, we found that patients with CLL had a higher expression of PD-1 transcript (PDCD1) than healthy volunteers (p < 0.0001). PDCD1 expression was comparable between CLL cells from accumulation (peripheral blood) and proliferation (bone marrow) disease compartments. In blood samples of patients with mutated IGHV genes PDCD1 expression was higher than with unmutated IGHV (p = 0.0299). We demonstrated that phosphorylation of SYK and LYN, key B-cell receptor signaling kinases, was independent of PD-1 expression in patients with CLL, while ZAP-70 phosphorylation in negative tyrosine residue 292 showed strong inverse correlation (r = − 0.8, p = 0.0019). No associations between five single nucleotide polymorphisms of PDCD1, their expressions and susceptibility to CLL were found. In conclusion, PD-1 might be an independent, universal marker of CLL cells and a part of their activated phenotype, and subsequently might modulate the function of ZAP-70.

Specific cytotoxic T-cell immune responses against autoantigens recognized by chronic lymphocytic leukaemia cells

Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia (CLL). Cytoskeletal proteins, including non‐muscle myosin heavy chain IIA (MYHIIA), vimentin (VIM) and cofilin‐1 (CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B‐cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase‐polymerase chain reaction

Budowa i funkcje jądrowego czynnika transkrypcyjnego NF kappa B (NF-κB) oraz jego znaczenie w przewlekłej białaczce limfocytowej

Streszczenie Jądrowy czynnik transkrypcyjny NF kappa B (NF-κB) pelni znaczącą role w procesach odpornościowych i zapalnych. Zdolnośc NF-κB do hamowania apoptozy, indukcji proliferacji oraz nasilania procesu angiogenezy sugeruje, ze NF-κB moze byc istotnym czynnikiem w procesie onkogenezy i progresji nowotworu. Przekaźnictwo sygnalu NF-κB w guzach litych, a takze w nowotworach hematologicznych, w tym w przewleklej bialaczce limfocytowej (PBL) jest stale poznawane. Biorąc pod uwage fakt, ze NF-κB jest niezbedny do przezycia komorek bialaczkowych, nalezy sądzic, ze moze stanowic on dobry cel terapeutyczny w PBL. w artykule przedstawiono aktualny stan wiedzy na temat struktury i funkcji bialek NF-κB, a takze mechanizmow ich aktywacji i znaczenia w PBL.

Indirect induction of regulatory T cells accompanies immune responses during peptide vaccination of chronic lymphocytic leukaemia patients.

Keywords: chronic lymphocytic leukaemia; thalidomide; T regulatory cells; interleukin 2; peptide vaccination