INTRODUCTION: It is widely accepted that expression of ZAP-70 in chronic lymphocytic leukemia (CLL) remains stable in time. However, data supporting this notion are surprisingly scarce. Therefore, we assessed expression of ZAP-70 in serial samples taken during the course of the disease. PATIENTS AND METHODS: We studied 44 patients with CLL diagnosed according to NCI-WG criteria (34 men, 10 women, median age 62, range, 36-81). A total of 104 samples were examined; all patients had at least two measurements. Median interval between the first and the second sample was 13 months (range, 2-36). ZAP-70 expression was detected by flow cytometry using phycoerythrin-conjugated monoclonal antibody clone 1E7.2 and negative isotype control. Twenty percent of positive cells were considered as the threshold of positivity. RESULTS: Significant change in ZAP-70 expression (i.e. from positivity to negativity and vice versa) was detected in 15/44 patients (34%). Interestingly, 7/8 patients whose ZAP-70 expression converted to positivity had unmutated IgVH genes. In addition, the conversion was accompanied by clinical progression or relapse in all but one patient. On the other hand, 5/7 patients with loss of ZAP-70 had stable clinical course. One patient became ZAP-70-negative during treatment with prednisone for autoimmune hemolytic anemia. CONCLUSIONS: In contrast to commonly accepted opinion, significant change in ZAP-70 expression in time was detected in a substantial proportion of our patients with CLL. While the conversion to ZAP-70 negativity was found predominantly in patients with stable disease, change to positivity was typical in patients with unmutated IgVH genes at the time of progression or relapse. Based on our pilot results, repeated assessment of ZAP-70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP-70-negative.

• MeSH
• chronická lymfatická leukemie enzymologie   etiologie   MeSH
• dospělí MeSH
• geny pro těžké řetězce imunoglobulinů MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery krev   MeSH
• pilotní projekty MeSH
• progrese nemoci MeSH
• protein-tyrosinkináza ZAP-70 krev   MeSH
• recidiva MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• protein-tyrosinkináza ZAP-70 MeSH
• ZAP70 protein, human MeSH Prohlížeč

Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patient's ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP-70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

• MeSH
• antigeny CD38 metabolismus   MeSH
• chromozomální delece MeSH
• chronická lymfatická leukemie diagnóza   genetika   metabolismus   patofyziologie   MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem metabolismus   MeSH
• geny pro těžké řetězce imunoglobulinů genetika   MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• patologická angiogeneze MeSH
• prognóza MeSH
• proteiny vázající RNA MeSH
• represorové proteiny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD38 MeSH
• CD38 protein, human MeSH Prohlížeč
• fosfotransferasy s alkoholovou skupinou jako akceptorem MeSH
• jaderné proteiny MeSH
• membránové glykoproteiny MeSH
• proteiny vázající RNA MeSH
• represorové proteiny MeSH
• YLPM1 protein, human MeSH Prohlížeč

CHOP chemotherapy has been used as a standard first-line treatment for diffuse large B-cell lymphoma since the 1970s. Phase III trials have shown that the addition of rituximab (R) to CHOP chemotherapy leads to significant improvements in response rate, progression-free survival and overall survival. This single-center, retrospective study was performed to evaluate the role of the addition of R to chemotherapy (CHT) in a real-world clinical setting. Outcomes were assessed in 85 patients with newly diagnosed DLBCL treated with CHT alone (n=38) and R-CHT (n=47). Complete response (CR) rates were significantly higher after R-CHT than CHT (93 % vs. 73 %; p=0.02). The relapse rate was significantly higher after CHT compared with R-CHT (38 % versus 12 %; p=0.01). Progression-free survival was significantly extended by the addition of R (median not reached versus 26.1 months; p=0.04). These data bring further support for rituximab-based immunochemotherapy as a standard first-line therapy for patients with DLBCL.

• MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• myší monoklonální protilátky MeSH
• prednison aplikace a dávkování   MeSH
• progrese nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   terapeutické užití   MeSH
• rituximab MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklofosfamid MeSH
• doxorubicin MeSH
• monoklonální protilátky MeSH
• myší monoklonální protilátky MeSH
• prednison MeSH
• rituximab MeSH
• vinkristin MeSH

Polycyclic aromatic hydrocarbons (PAH) represent a group of ubiquitous environmental pollutants. Their toxic effects are demonstrated mainly in tissues with high proliferation. The direct distribution of PAH in non-metabolized form to bone marrow and their biotransformation at this site to the toxic metabolites is necessary for demonstration of their toxic effect here. CYP1B1 that is constitutive expressed by stromal cells plays probably the main role in biotransformation of PAH in bone marrow. Reactions of toxic metabolites, development of oxidative stress and interference with intracellular calcium are ranged between the most important mechanisms of structural and functional changes of bone marrow after exposure to PAH. Pathological induction of apoptosis and malignant transformation of stem cells represent the concrete forms of bone marrow damage, caused by exposure to PAH. The bone marrow constitutes the central organ of hematopoiesis and the sites of production of cells of immune system. Its damage can bring therefore crucial health consequences for the whole organism.

• MeSH
• kostní dřeň účinky léků   MeSH
• látky znečišťující životní prostředí škodlivé účinky   farmakokinetika   farmakologie   MeSH
• lidé MeSH
• polycyklické aromatické uhlovodíky škodlivé účinky   farmakokinetika   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• látky znečišťující životní prostředí MeSH
• polycyklické aromatické uhlovodíky MeSH