[Show abstract][Hide abstract] ABSTRACT: The inhibitors of apoptosis proteins (IAPs) are involved in apoptosis regulation, cell signaling and cell division. The IAPs have been divided into three classes based on the presence, or absence, of a RING zinc finger (RZF) and the homology of their BIR (baculoviral- IAP-repeat) domains. Class III IAPs contain two members: survivin and BRUCE. BRUCE (also known as apollon, or BIRC 6) is a large protein (528- kDa) that contains single BIR and ubiquitin- conjugating enzyme (UBC) domains at the N- and C-termini respectively. BRUCE ubiquitinates and facilitates proteasomal degradation of two IAPs antagonists serine protease HtrA2 and Smac (second mitochondria- derived activator of caspases), as well as caspase-9. Cytosolic, mature Htr A2 and Smac eliminate the ability of IAPs to inhibit caspases, thereby enhancing caspases activation and apoptosis.
No preview · Article · Jan 2006 · Acta haematologica Polonica
[Show abstract][Hide abstract] ABSTRACT: Fluorescence in situ hybridization (FISH) technique was used in the analysis of peripheral blood cells of 41 non-treated patients with B-cell chronic leukemia (B-CLL) in 0 and 1 Rai stages, taking into account the TP53 gene deletion, 13q14 deletion, 11q23 deletion, the ATM gene deletion, and trisomy 12. According to the presence or absence of the TP53 gene deletion, the patients were divided into two groups. Group I with clonal TP53 deletion comprised 13 patients (32%), where the percentage of cells with TP53 deletion was even or higher than 10% (median, 13%). The results show that TP53 deletion in a relatively large group of B-CLL patients may be found at the early stage of the disease. Group II, without clonal TP53 deletion, comprised 28 patients 68%), with a median of aberrant cell percentage of 3%. In two subjects of Group I, and three patients of Group II, FISH analysis was repeated (after 12 to 43 months), and an increase in the percentage of cells with TP53 deletion. In both groups of patients, one or two aberrations, i.e. 13q14 deletion, 11q23 deletion, ATM deletion and chromosome 12 trisomy, were additionally found. This indicates genome instability in B-CLL patients. In subjects with higher percentages of cells with TP53 deletion, disease progression was more frequently observed, indicating that the presence of TP53 deletion is an unfavorable prognostic factor, especially if it is associated with 11q23 deletion or ATM deletion.
[Show abstract][Hide abstract] ABSTRACT: Fetal and embryonic tissues show high expression of survivin, while it is undetectable in most normal, fully differentiated adult tissues. This is in marked contrast to high levels of expression observed in a broad range of malignancies. The cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a useful diagnostic marker of cancer and a potential target for cancer treatment. Survivin is also involved in vascular injury and its healing.
No preview · Article · Jan 2005 · Acta haematologica Polonica
[Show abstract][Hide abstract] ABSTRACT: Survivin is the smallest known member of apoptosis inhibiting proteins (IAPs) family. Structurally it is composed of a single BIR domain and extended C-terminal α-helical coiled-coil domain, without a RING finger. Survivin inhibits apoptosis via its BIR domain by either directly or indirectly interfering with the function of caspases. The α-helical coiled-coil domain of survivin is involved in interaction with microtubulin. Survivin also plays critical role in regulating the cell cycle and mitosis.
No preview · Article · Jan 2005 · Acta haematologica Polonica
[Show abstract][Hide abstract] ABSTRACT: The crucial role of mitochondria in the initiation of apoptosis is well established. The metabolic consequences of mitochondrial membrane permeabilization as well as the leakage of apoptogenic factors normally confined to mitochondria determines the catabolic features of cell death. Here we attempt to summarize the current view of the mechanisms that lead to the efflux of many proteins from mitochondria during apoptosis and the role played by Bcl-2 family proteins in these events.
No preview · Article · Feb 2004 · Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine)
[Show abstract][Hide abstract] ABSTRACT: In a group of 75 untreated patients with a typical B cell chronic lymphocytic leukaemia (B-CLL) (CD19+, CD5/CD19+, CD23/CD19+), the frequency and clinical significance of TP53 gene deletion and chromosome 12 trisomy were assessed. The studies of peripheral blood lymphocytes were conducted using interphase in situ hybridization technique. Clonality was identified when TP53 deletion or chromosome 12 trisomy was found in at least 10% of cells. From all 75 examined patients 32 individuals without any of the genetic aberrations were analyzed (Group I) and 30 subjects with TP53 deletion (Group II) were chosen. In the other 13 patients, discussed in the next paper, either chromosome 12 trisomy (Group III--seven subjects) or both chromosome 12 trisomy and TP53 deletion (Group IV--six subjects) were found. In the Group I, there has been no further contact with three patients, while in the Group II--with two individuals. In the Group I, one patient of 29 in the study (3%) died after 84 months (seven years) from the diagnosis, whereas in the Group II--nine subjects of 28 in the study (32%) died within 1-36 months from the diagnosis. In three of those patients in the terminal condition, cytogenetic studies were repeated revealing an increase of approximately 5% in the percentage of peripheral blood cells with TP53 deletion. The frequent presence of TP53 deletion detected in 48% of patients is surprising. It is generally thought that the aberration is found in 10-15% of clinical cases. The studies should be confirmed on a larger group of patients.
No preview · Article · Jan 2004 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: Among 75 untreated patients with typical (CD19+, CD5/CD19+, CD23/CD19+) B-cell chronic lymphocytic leukemia (B-CLL) cytogenetic aberrations of peripheral blood cells were evaluated, using fluorescence in situ hybridization techniques. Two cytogenetic aberrations were evaluated: trisomy 12 and TP53 deletion. The clonality was determined when > or = 10% of the cells had of trisomy 12 or deletion TP53 gene. Trisomy 12 in 7 patients was detected, while trisomy 12 and TP53 deletion simultaneously in 6 patients were present. If the first group will be linked to the second one then 13 patients among 75 (17%) will have trisomy 12. In group of patients with trisomy 12 and TP53 deletion percentage of cells with trisomy 12 was almost two time more compare to patients with trisomy 12 as a single aberration. It is possible, that TP53 deletion ("the guardian of the genome") facilitates proliferation clones with others genomic aberrations. In two patients with trisomy 12 control cytogenetic study was performed. Increase of percentage cells with trisomy 12 for 8% and 30% respectively was detected. However, proliferation of cells with TP53 deletion was observed too. Clinical course of B-CLL in group of patient with trisomy 12, trisomy 12 and TP53 deletion simultaneously is more aggressive compared to the course of disease of patients with no cytogenetic aberrations (patients of Group I from Part I of paper). Frequency of IGHV gain mutation occurrence was not analyzed in both groups of patients. But trisomy 12 together with unmutated IGHV gene is found by some authors. The absence IGHV gene mutation is independent unfavourable prognostic factor.
No preview · Article · Dec 2003 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: Members of the tumor necrosis factor (TNF) family have been shown to be key mediators in the formation and regulation of normal B-cell responses. B-lymphocyte stimulator - BLyS (BAFF, THANK, TALL-1 and zTNF-4) is a newly identified TNF family member expressed by monocytes, macrophages and dendritic cells, but not by B cells. BLyS is a type II membrane protein that acts in either a membrane-bound form or proteolytically cleaved into a soluble cytokine. BLyS protects peripheral B cells from apoptosis and enhances cell survival. Attenuation of apoptosis by BLyS correlates with changes between Bcl-2 family proteins in favor of cell survival. Attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity, as well as the physiologic humoral immune response. Transgenic mice overexpressing BLyS in lymphoid cells develop symptoms characteristic of systemic lupus erythematosus and expand a rare population of splenic B1a lymphocytes (CD5+). Overexpression of BLyS activates the NF-κB, ELK-1, c-Jun NH2-terminal kinase and p38 mitogen-activated protein. Three receptors including B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and B cell-activating factor-receptor (BAFF-R) have been identified as receptors for BLyS. In contrast to BLyS, the receptors of BLyS are expressed on normal B cells and B-cell chronic lymphocytic leukemia (B-CLL) cells. In addition, B-CLL cells from a subset of patients abnormally express BLyS mRNA.
No preview · Article · Jan 2003 · Acta haematologica Polonica
[Show abstract][Hide abstract] ABSTRACT: Uncontrolled cell proliferation is the hallmark of cancer, and tumour cells have typically acquired damage to genes that directly regulate their cell cycles. Genes that link checkpoint controls to cancer and other related genetic disease include the TP53 and ATM genes. The abnormalities of these genes are clearly associated with particular forms of the B-cell chronic lymphocytic leukemia and poor prognosis.
No preview · Article · Feb 2001 · Postȩpy higieny i medycyny doświadczalnej
[Show abstract][Hide abstract] ABSTRACT: Intravascular lymphoma (IVL) is characterized by proliferation of large malignant lymphoid cells within the lumen of small vessels. Sites usually affected include the central nervous system and skin althoug involvement of multiple organ symptoms have been described. IVL is very rare and aggressive type of lymphoma. Based on review of the literature we present clinicopathological, immunohitochemical and molecular features of the IVL. The etiological possibilities are discussed. Key words: intravascular malignant lymphoma, immunophenotype, histopathological and clinical presentation, etiological possibilities
No preview · Article · Oct 2000 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: CD43 is an integral cell membrane mucin appearing on hematopoietic cells in embryonic life probably on cells of vitellus bag, in embryonic and foetal liver and in foetal bone marrow. In adults CD43 occurs both on bone marrow hematopoietic stem cells as well as on peripheral mature white blood leukocytes with the exception of resting B lymphocytes. CD43 is also found on tissue macrophage, dendritic cells, smooth muscle cells, epithelium and endothelium. CD43 expression was detected on cells of leukaemias myeloid and lymphoid, lymphoma cells and metastases of solid neoplasms. Due to the elongated, twig-resembling shapes and numerous negatively charged rests of sialic acid CD43 can act in an anti-adhesive fashion e.g., disturbing ICAM-1 (CD54)--LFA-1 (CD11A/CD18) interaction. Alternatively, in certain conditions CD43 can be pro-adhesive. So, e.g., adhesion hematopoietic progenitor cells to stromal bone marrow cells partly depends on CD34-CD43 cooperation. Similarly, according to the degree of cell maturity and the kind of cell line, CD43 can induce either activation or cell apoptosis. So, bindig CD43 by specific monoclonal antibody induces activation and proliferation of T cells and also the oxidation burst of monocytes and neutrophils. On the other hand, CD43 induces apoptosis, especially in dividing progenitor hematopoietic stem cells.
No preview · Article · Feb 2000 · Postȩpy higieny i medycyny doświadczalnej
[Show abstract][Hide abstract] ABSTRACT: CD43 (other names: sialophorin, leukosialin, sialoglycoprotein of white blood cells) is an integral cell membrane mucin. In population of peripheral B cells CD43 occurs only on activated B cells and CD5 positive B cells. These last cells create neoplasm population in patients with B-cell chronic lymphocytic leukemia (B-CLL). Anti-CD43 monoclonal antibodies are used routinely in investigations of tissue fragments in cases of non-Hodgkin's lymphoma, whereas we did not find publication on theme of CD43 expression on peripheral blood B cells in patients with B-cell chronic lymphocytic leukemia. Wherefore advisable appeared estimation CD43 expression on B-CLL cells and comparison it with expression of typical B-CLL markers--such as CD5 and CD6. Immunological phenotype of peripheral blood and bone marrow lymphocytes has been evaluated using flow cytometry (Cytoron Absolute Ortho-Diagnostic Systems) and two-color staining. Twenty six untreated patients with B-CLL were studied. Because on well-known correlations between CD43 expression and metastasis potential of tumor, patients were divided on two groups differing score of total tumor mass (score TTM). Score TTM was evaluated according to criterion of Jaksic and Vitale. Twelve patients whose TTM score was equal or lower than 9 and median lymphocytosis was 24.6 x 10(9) in microliter were included in group I. 14 patients whose TTM score was higher than 9 were included in group II. Median lymphocytosis in these patients was 152.6 x 10(9) in microliter. The median percentage of CD43+/CD19+ cells in peripheral blood was 62.6% in the group I, and 75% in the group II (p < 0.05). Median fluorescence intensity (MFI) of CD43 antigen was 87.7 in the I group comparing to 77.4 in the group II. So one observed tendency to lowering MFI during tumor growing but the difference was not significant (p = 0.25). In peripheral blood during progression of disease more clearly than CD43+ cells increased percentage of CD5+ and CD6+ cells. The median percentage of CD19+/CD5+ cells was 62.7% in the group I, 82.4% in the group II and the difference was significant (p < 0.002). The difference in the median percentages CD6+/CD19+ cell 71.8% in group I and 84.3% in the II one were also significant (p < 0.03). MFI of CD5 and also CD6 antigens did not change in course of disease. Moreover, examination of CD43 and CD5 expression in marrow additionally to blood study were performed in 12 cases (6 from group I, 2 from group II and 4 new not included). The median percentage of CD43+/CD19+ cell was 35.1% in blood and 43.7% In marrow, in contrast to these results was the median percentage of CD19+/CD5+ cell, which was higher in peripheral blood (70.4%) than in bone marrow (60.9%). The results of this study indicate that CD43 is present on peripheral blood B-CLL cells. Moreover, percentage of these cell increases during progression of disease however more weakly than percentage of CD5 and CD6 positive cells. Expression of CD43 is independent from expression CD5 and CD6 and diminishes during tumor mass increasing, what can depended from releases exocellular domains of CD43. CD43+ cell from B-CLL patients have a tendency to accumulation in tissues what is illustrated by higher percentage of CD43+ cell in bone marrow than in peripheral blood.
No preview · Article · Sep 1999 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: Antigen CD5 is the glycoprotein which belong to the scavenger receptor cysteine-rich family. Mainly there is on the T cells subpopulation. During fetal life B CD5+ cells are major subpopulation of B cells in the spleen, lymph nodes and there are also in the cord blood. In adult CD5+ cells are minor subpopulation (27%) of B cells from the peripheral blood. CD5 there are on chronic lymphocyte leukaemia B cells (B-CLL) also. Usually expression CD5 on B-CLL cells associated with weak or lack expression of the surface immunoglobulins and CD79 beta, CD20, CD22, CD21 (CR-2), CD35 (CR-1) antigens. It appeared interesting to compare the expression of CD5 antigen (the mean fluorescence intensity--MFI of CD5) on B cells from the cord blood, adults peripheral blood and B-CLL patients. MFI of CD5 on B and T cells were also compared in each groups. MFI of CD 19 was studied too. Lymphocytes from the cord blood (11 assays), adult peripheral blood of healthy volunteers (18 assays) and the peripheral blood of no treated patients with B-CLL (56 assays) were studied. The immunological phenotype of lymphocytes was evaluated with the monoclonal antibodies anti-CD5 and anti-CD19 by the flow cytometry method. We have demonstrated that MFI of CD5 on B cells from patients with B-CLL was strongest and weakest from normal individuals. MFI of CD5 on T cells from patients with B-CLL is stronger in comparison to healthy volunteers. MFI of CD19 is weakest on cells from patients with B-CLL and strongest in normal individuals. On the basis of the our results and other medical papers we suggest on the one hand that biology of B-CLL depend on deficit antigens specific for B cells lines on the other hand depend on overexpression of CD5 antigens on leukaemic B and T cells also.
No preview · Article · May 1999 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: Heterogeneity of B-cell chronic lymphocytic leukemia (B-CLL) may by partial an explanation of the ability of CLL cells to interact with the environment and it seems to be not related exclusively to cytogenetic abnormalities. For this reason T cell subpopulations were analysed in bone marrow and peripheral blood in two selected groups of B-CLL patients. These groups differed significantly in percentages of CD4+ helper T cells in bone marrow. In the first group (11 patients) percentage of CD4+ cells was higher than 9 p.c., in the second (10 patients) this percentage was equal, or lower than 2 p.c. Moreover these groups differed also in total tumor mass score (TTM-score) according to the criteria of Jaksić and Vitale. TTM-score in the first group was 9.7 in the second--22.9. In the first group CD4- cells predominated over CD8+ cytotoxic suppressor cells, as well as CD4+ CD45RO+ helper-inducer cells predominated over CD4+ CD45RA+ suppressor-inducer cells. In the second group we observed some superiority of CD8+ and CD4+ CD45RA+ cells. We can speculate that the predominance of CD4+ and CD4+ CD45RO+ cells over CD8+ and CD4+ CD45RA+ cells in bone marrow facilitate the proliferation or inhibits the apoptosis of CLL cells when the TTM-score is small. On the contrary when the TTM-score is larger, than the leukemic cells expanded in bone marrow without concomitant helper cells.
No preview · Article · Jan 1999 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: Antigen CD5 is the glikoprotein which belong to the scaveneger receptor cysteine-rich family. Mainly there is on the T cells subpopulation. During fetal life B CD5 + cells are major subpopulation of B cells in the spleen, lymph nodes and there are also in the cord blood. In adult CD5 + cells are minor subpopulation (27%) of B cells from the peripheral blood. CD5 there are on chronic lymphocyte leukaemia B cells (B-CLL) also. Usually expression CD5 on B-CLL cells associated with weak or lack expression of the surface immunoglobulins and CD79 beta, CD20, CD22, CD21 (CR-2), CD35 (CR-1) antigens. It appeared interesting to compare the expression of CD5 antigen (the mean fluorescence intensity-MFI of CD5) on B cells from the cord blood, adults peripheral blood and B-CLL patients. MFI of CD5 on B and T cells were also compared in each groups. MFI of CD 19 was studied too. Lymphocytes from the cord blood (11 assays), adult peripheral blood of healthy volunteers (18 assays) and the peripheral blood of no treated patients with B-CLL (56 assays) were studied. The immunological phenotype of lymphocytes was evaluated with the monoclonal antibodies anti-CD5 and anti-CD19 by the flow cytometry method. We have demonstrated that MFI of CD5 on B cells from patients with B-CLL was strongest and weakest from normal individuals. MFI of CD5 on T cells from patients with B-CLL is stronger in comparison to healthy volunteers. MFI of CD19 is weakest on cells from patients with B-CLL and strongest in normal individuals. On the basis of the our results and other medical papers we suggest on the one hand that biology of B-CLL depend on deficit antigens specific for B cells lines on the other hand depend on overexpression of CD5 antigens on leukaemic B and T cells also.
[Show abstract][Hide abstract] ABSTRACT: CD8 antigen is present on the surface of cytotoxic-suppressor T cells, NK cells and majority of thymocytes. Expression of CD 8 is associated with CD 3 antigen, which is a part of a T cell receptor. However, CD 8 antigen is undetectable on normal B cells. In sporadic cases of B cell-chronic lymphocytic leukaemia (B-CLL) it was found on leukaemic B cells. We report a case of B-CLL of benign course with CD19+, CD5+, CD40+, CD19+, CD20+, CD19+, CD19+HLADR+ leukaemic cells expressing CD8 antigen on CD19+ leukaemic cells. It seems that original neoplasms source was localized out of bone marrow. We suggest that the origin of the target cell for neoplasms transformation could be CD5+ B cell and CD8+ T cell gamma + delta + CD8+.
No preview · Article · Feb 1998 · Polskie archiwum medycyny wewnȩtrznej
[Show abstract][Hide abstract] ABSTRACT: The average dosage of radiation which was measured in Poland during the year after damage of the nuclear power in Chernobyl (according to UNSCEAR) was 0.27 mSv, which gives 11% natural radiation dosage in the period of one year (2.6 mSv). Disturbances of cells genome caused by radiation are possible because of big dosage of radiation in Lublin region. It was interesting to define morbidity and mortality of multiple myeloma (MM) after the damage in Chernobyl. The average latent period of MM is about 20 years (like thyroid carcinoma). The increase of thyroid carcinoma morbidity after the damage of Chernobyl nuclear power plant in Byelorussia. Ukraine, Russia was observed. The increased morbidity rate of MM among patients of Haematologic Department (especially in the third stage of disease) and the increased mortality rate in Lublin region was confirmed.
No preview · Article · Jun 1997 · Polskie archiwum medycyny wewnȩtrznej