The Prognosis of Adult Burkitt's Cell Leukemia in Real-Life Clinical Practice.

OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. MATERIALS AND METHODS: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups. RESULTS: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients. CONCLUSION: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.

OBJECTIVE: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. MATERIALS AND METHODS: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. RESULTS: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. CONCLUSION: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

Pharmacobiological Approach for the Clinical Development of Ruxolitinib in Myeloproliferative Neoplasms.

Ruxolitinib, a JAK1 and JAK2 inhibitor drug, has recently been approved for the treatment of patients with high- or intermediate-risk myelofibrosis with symptomatic splenomegaly. Ruxolitinib is the first clinically useful targeted therapy in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). The aim of this paper is to indicate pharmacobiological aspects of ruxolitinib within the potential context of MPNs. Pharmacobiological assessments, in addition to knowledge of the risk profile for ruxolitinib in MPNs, are required. We propose hypotheses based on our experience in a splenectomized MPN patient with hyperproliferative bone marrow and moderate fibrosis receiving ruxolitinib. We believe that a true clinical development approach for this drug should include pharmacobiological assessments for ruxolitinib in addition to the disease risk profile of MPNs.

Local Renin-Angiotensin system in normal hematopoietic and multiple myeloma-related progenitor cells.

OBJECTIVE: The prominent functions of the local renin-angiotensin system (RAS) in primitive hematopoiesis further support the hypothesis that local autocrine bone marrow RAS could also be active in neoplastic hematopoiesis. The aim of this study is to examine critical RAS elements in normal CD34+ hematopoietic stem cells and multiple myeloma (MM)-related progenitor cells. MATERIALS AND METHODS: The study group comprised the total bone marrow cells (CBM) of 10 hematologically normal people, the CD34+ stem cell samples (CD34+CBM) of 9 healthy donors for allogeneic peripheral stem cell transplantation, and the CD34+ stem cell samples (CD34+MM) of 9 MM patients undergoing autologous peripheral stem cell transplantation. We searched for the gene expression of the major RAS components in healthy hematopoietic cells and myeloma cells by quantitative real-time polymerase chain reaction analysis. RESULTS: RENIN, angiotensinogen (ANGTS), and angiotensin converting enzyme-I (ACE I) mRNA expression levels of CBM were significantly higher than those in myeloma patients (p=0.03, p=0.002, and p=0.0008, respectively). Moreover, RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01). However, ACE I expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89). CONCLUSION: Although found to be lower than in the CBM and CD34+CBM hematopoietic cells, the local RAS components were also expressed in CD34+MM hematopoietic cells. This point should be kept in mind while focusing on the immunobiology of MM and the processing of autologous cells during the formation of transplantation treatment protocols.

Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic hematopoietic stem cell transplantation for acute leukemia patients: a single center experience.

Due to the high transplant related morbidity and mortality (TRM), relatively younger acute leukemia patients that have a good performance status and no comorbidity are eligible for myeloablative conditioning (MAC) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcomes of 84 consecutive adult patients with ALL (n=38) or AML (n=46) who underwent allo-HSCT from their HLA-identical siblings were evaluated retrospectively. The median age at transplantation was 34 (17-58 years) for the whole patient population. Of these, 24 patients received a MAC and 60 patients received a fludarabine-based reduced intensity conditioning regimen (RIC). After a median follow-up of 32 months (range, 1-119), for the entire group, the 3-year estimated overall survival (OS) was 57.5% and the disease-free survival (DFS) was 51.5%. The OS for ALL and AML patients were 53.9% vs 62.1%: and DFS were 50.5% and 53.4%, respectively. The 3-year estimated OS for RIC and MAC patients were 63.2% and 41.7%; and DFS were 57.1% and 34.7%, respectively. In ALL patients, conditioning regimens (RIC vs MAC) led to similar OS and DFS; however, in AML patients both OS (70.1% vs 21.4%) and DFS (59.3% vs 42.9%) were found to be higher in RIC patients compared to MAC recipients. Overall, the TRM at day 100 was 1.7% and has increased up to 5.1% at 1st year. In multivariate analysis, the diagnosis (p=0.03) and RIC regimen (p=0.027) were the prognostic variables for prolonged OS in all patients; and RIC regimen (p=0.031) was the only prognostic factor for prolonged OS in AML patients. The first complete remission (CR1) was correlated with a prolonged DFS as an independent variable for all patients (p=0.09). Eleven of the RIC patients (18.3%) and 6 of the MAC patients (25%) developed acute graft-versus-host disease (GvHD). Seventeen of the RIC patients (33.3%) and 4 of the MAC patients (16.7%) developed chronic GvHD. In conclusion, RIC conditioning regimens may provide a longer OS and DFS, especially in patients with AML who are in first CR, not eligible for MAC conditioning.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

EUTOS CML prognostic scoring system predicts ELN-based 'event-free survival' better than Euro/Hasford and Sokal systems in CML patients receiving front-line imatinib mesylate.

OBJECTIVES: The validity of the three currently used chronic myeloid leukemia (CML) scoring systems (Sokal CML prognostic scoring system, Euro/Hasford CML scoring system, and the EUTOS CML prognostic scoring system) were compared in the CML patients receiving frontline imatinib mesylate. PATIENTS AND METHODS: One hundred and fourty-three chronic phase CML patients (71 males, 72 females) taking imatinib as frontline treatment were included in the study. The median age was 44 (16-82) years. Median total and on-imatinib follow-up durations were 29 (3.8-130) months and 25 (3-125) months, respectively. RESULTS: The complete hematological response (CHR) rate at 3 months was 95%. The best cumulative complete cytogenetic response (CCyR) rate at 24 months was 79.6%. Euro/Hasford scoring system was well-correlated with both Sokal and EUTOS scores (r = 0.6, P < 0.001 and r = 0.455, P < 0.001). However, there was only a weak correlation between Sokal and EUTOS scores (r = 0.2, P = 0.03). The 5-year median estimated event-free survival for low and high EUTOS risk patients were 62.6 (25.7-99.5) and 15.3 (7.4-23.2) months, respectively (P < 0.001). This performance was better than Sokal (P = 0.3) and Euro/Hasford (P = 0.04) scoring systems. Overall survival and CCyR rates were also better predicted by the EUTOS score. DISCUSSION: EUTOS CML prognostic scoring system, which is the only prognostic system developed during the imatinib era, predicts European LeukemiaNet (ELN)-based event-free survival better than Euro/Hasford and Sokal systems in CML patients receiving frontline imatinib mesylate. This observation might have important clinical implications.

Review of therapeutic options and the management of patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a poorly understood group of disorders caused by one or more genetic aberrations in the bone marrow-derived cell line responsible for hematopoiesis. Recent advances in genetic medicine have offered new insights into the epigenesis as well as the prognosis of MDS, but have not resulted in new or improved curative treatment options. Bone marrow transplantation, introduced before the advent of genetic medicine, is still the only potential cure. Advances in other medical and pharmaceutical areas have broadened the scope of supportive care and disease-modifying therapies, and treating physicians now have a broad range of disease management options depending on a patient's likely prognosis. There is now clear evidence that appropriate supportive care and therapeutic intervention can improve progression-free and overall survival of MDS patients.

Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders.

There is preliminary evidence that the local renin-angiotensin system (RAS) could affect neoplastic hematopoiesis. The aim of this study is to search messenger RNA (mRNA) expressions of the essential RAS elements in myeloid and lymphoid hematological neoplastic disorders. Forty-six patients with newly diagnosed myeloid (AML, biphenotypic leukemia, CML) or lymphoid (CLL, NHL, B-ALL, T-ALL) hematological disorders were included in the study. In the lymphoid group, the median expression values of RENIN, ACE1, ACE2 and ANGIOTENSINOGEN (ANGTS) mRNAs were 1.96%, 0.42%, 0.00% and 0.00%, respectively; in the myeloid group, 0.73%, 1.55%, 0.04% and 0.006%, respectively. In the lymphoid group, RENIN levels were significantly higher (p = 0.001), whereas ACE1 and ACE2 levels were significantly higher in the myeloid group (p values were 0.013 and 0.010, respectively). ANGTS levels were similar in both groups. In patients with non-ALL lymphoid malignancies, RENIN expressions were significantly higher when compared to ALL patients (p = 0.004). All patients with active disease had significantly higher RENIN mRNA expression levels than patients without active disease (2.03% vs 0.30%) (p = 0.034). The result of our present study indicates that the activities of local RAS may differ in distinct disease states such as leukemia and lymphomas.

Co-expression of t(15;17) and t(8;21) in a Case of Acute Promyelocytic Leukemia: Review of the Literature.

UNLABELLED: Additional chromosomal abnormalities in acute myelogenous leukemia have been identified as one of the most important prognostic factors. Favorable chromosomal changes such as t(8;21), inv(16), and t(15;17) are associated with higher rates of complete remission and event-free survival. Translocation (15;17) characterizes acute promyelocytic leukemia (APL) (French-American-British class M3) in almost all patients. Secondary chromosomal abnormalities are also present in approximately 23%-29% of patients with newly diagnosed APL. The prognostic implications of t(8;21) and other secondary cytogenetic aberrations in APL are reviewed here. We present a 47-year-old woman diagnosed with APL whose initial cytogenetic analysis included both t(8;21) and t(15;17). The initial induction chemotherapy included 3 days of idarubicin (12 mg/m2/day) and daily all-trans retinoic acid (ATRA; 45 mg/m2/day). At the sixth week of treatment, a control bone marrow biopsy was found to be normocellular, t(15;17) bcr3 and t(8;21) were negative, and t(15;17) bcr1 fusion transcripts were reduced from 5007 (1.78525699%) copies per 1 µg RNA to 40 (0.00062020%) with real-time quantitative polymerase chain reaction. Consolidation with 4 days of idarubicin (5 mg/m2/day), ATRA (45 mg/m2/day for 15 days), and cytarabine (1 g/m2/day for 4 days) was then started. However, the patient became pancytopenic and had neutropenic fever after consolidation treatment. Unfortunately, she died 3 months after the time of APL diagnosis, due to acute respiratory distress syndrome-like respiratory problems and multiorgan dysfunction requiring respiratory support and hemodialysis. CONFLICT OF INTEREST: None declared.

A comparison of Jurkat cell-reactive anti-T lymphocyte globulin and fetal anti-thymocyte globulin preparations in the treatment of aplastic anemia.

OBJECTIVE: The aim of this study was to investigate the success rate and effects on survival of different anti-thymocyte globulin (ATG) preparations in patients diagnosed with aplastic anemia. SUBJECTS AND METHODS: Of the total 24 patients included in the study, 12 were male and 12 female with a median age of 44 years (range 16-72). Nine patients received Lymphoglobulin®, 7 Thymoglobulin® and ATG-Fresenius® (ATG-F). There was no significant difference between the three treatment groups in terms of severity of aplastic anemia. RESULTS: The estimated 6-month survival rates for ATG-F, Lymphoglobulin and Thymoglobulin groups were 42.9, 77.8 and 71.4%, respectively. The difference in overall survival rates between groups was not significant, most likely due to the low number of patients. The most striking result was that none of the patients in the ATG-F preparation group showed any response to treatment. The ATG-F group was found to have a significantly inferior response rate (p = 0.07). CONCLUSION: Our data showed that none of the patients responded to ATG-F treatment. Hence, despite the small number of the patients, we recommend that ATG-F should not be used for treatment of severe aplastic anemia.

[Investigation of West Nile virus seroprevalence in Hacettepe University Hospital blood donors and confirmation of the positive results by plaque reduction neutralization test]. / Hacettepe Üniversitesi Hastanesi Kan Donörlerinde Bati Nil Virusu Seroprevalansinin Arastirilmasi ve Pozitif Sonuçlarin Plak Redüksiyon Nötralizasyon Testi ile Dogrulanmasi

West Nile virus (WNV), a member of Flaviviridae family, is an enveloped, icosahedral, single-stranded positive-sense RNA virus. WNV is transmitted to humans by infected mosquitoe (especially Culex spp.) bites and cause a variety of clinical outcomes, ranging from asymptomatic infection to severe meningoencephalitis. The aims of this study were to determine and confirm the WNV seroprevalence in a chosen healthy population and to provide epidemiological data for Turkey about the recent status of the infection at our region. A total of 1200 serum samples collected from blood donors (400 were female, 800 were male; age range: 18-61 years, mean age: 37.8) who were admitted to Hacettepe University Hospital Blood Donation Center between April to December 2009, were included to the study. The presence of WNV IgG antibodies were screened by ELISA (Euroimmun, Germany), and the positive samples have been further investigated by WNV IgG avidity test in order to estimate the time of encounter to the virus. Indirect immunofluorescence antibody (IFA) test (Euroimmun, Germany) and plaque reduction neutralization test (PRNT) which is accepted as the reference method, were performed for the confirmation of WNV IgG positive results. Nineteen (1.6%) of the samples yielded WNV IgG positivity with ELISA, and all of which were IgGs with high avidities (Avidity index values were between 67.8-99.2%). Eight of 19 (42.1%) WNV ELISA IgG positive donors, had risk factors such as joining outdoor activities, contact with mosquitos and ticks and consuming raw milk and milk products. Of 19 samples that were taken into confirmation tests, 15 (78.9%) were found positive with IFA, and 10 (52.6%) were found positive with PRNT. WNV antibody positivity of 10 samples were then confirmed by PRNT, however eight samples which were found positive with both ELISA and IFA yielded negative results with PRNT. This data might indicate that ELISA and IFA methods in which virus-infected cells were used as substrates, have detected non-neutralizing antibodies against viral nucleocapsid antigens rather than the neutralizing antibodies detected against envelope glycoproteins by PRNT method. One sample which yielded low positive result only by ELISA test has been evaluated as a specificity issue of the test. As a result, the positivity rate (19/1200; 1.6%) of WNV IgG detected by ELISA in blood donors, has been confirmed as 0.8% (10/1200) by a gold standard method, PRNT. The data of this study indicated that the prevalence of WNV infections, although low in our region, deserves attention to be considered in surveillance and control programs related to WNV in Turkey.

Multiple bulky cutaneous plasmacytomas with CNS relapse without bone marrow involvement during the course of a lambda light chain myeloma.

BACKGROUND: Primary cutaneous plasmacytomas, a localized collection of neoplastic plasma cells, may present without bone marrow involvement. Secondary plasmacytomas can complicate the clinical course of multiple myeloma (MM). Both types of cutaneous plasmacytoma are commonly observed in the terminal stages of MM. CASE REPORT: We present the case of a 37-year-old Turkish man diagnosed with lambda light chain MM. The patient had numerous firm plaque-shaped cutaneous lesions on the left side of the chest, the left shoulder, and the right preauricular region without concurrent bone marrow disease. Histopathological examination of the cutaneous plaque on the left side of the chest revealed neoplastic plasma cells infiltrating the dermal region. Furthermore, the cytologic examination of cerebrospinal fluid disclosed lymphoplasmacytic cells. The patient was treated with VDTPACE (bortezomib + dexamethasone + thalidomide + adriamycin + cyclophosphamide + etoposide), and the cutaneous lesions disappeared. Central nervous system involvement was treated with craniospinal irradiation and intrathecal chemotherapy. CONCLUSION: Cutaneous involvement of MM is an unusual clinical presentation, but a high level of suspicion is advisable in patients with MM and skin lesions. The involvement of the skin was associated with advanced disease status and, therefore, with a poor prognosis. This is the first reported case of cutaneous involvement of lambda light chain MM.

Biphenotypic acute leukemia treated with acute myeloid leukemia regimens: a case series.

This study retrospectively analyzed 8 cases of biphenotypic acute leukemia (BAL) in respect of morphology, immune phenotype, karyotype, and clinical manifestations. Six patients had myeloid plus T lymphoid, and 2 cases had myeloid plus B-lymphoid immune phenotypic markers. Because selection of an antileukemic chemotherapy regimen for acute leukemia is largely based on whether a case is classified as myeloid or lymphoid, the presence of markers for both lineages may have important implications for treatment. However, there is no consensus yet on chemotherapy for patients with BAL. All of our patients were treated with regimens designed for acute myeloid leukemia (AML). Five patients were treated with high-dose cytarabine plus mitoxantrone and 3 achieved complete remission. Two patients treated with idarubicin plus cytarabine. Both of them achieved complete remission. One case was given cytarabine plus mitoxantrone and achieved complete remission. Consequently, 6 out of 8 BAL patients achieved complete remission with AML-type regimens.

Transformation of adult myelodysplastic syndrome-refractory anemia to acute T-cell lymphoblastic leukemia.

OBJECTIVE: Myelodysplastic syndrome (MDS) is recognized as a preleukemic disorder with a variable risk of transformation to acute myeloid leukemia. Usually the blast cells in leukemia are transformed after MDS displays a myeloid phenotype. Lymphoid progression had been reported as myeloid-lymphoid hybrid or early B phenotype, but our patient transformed acute T-lymphoblastic leukemia, which is a rare lymphoid transformation. CLINICAL PRESENTATION AND INTERVENTION: We present a case of refractory anemia with excess of blast that transformed into acute T-cell lymphoblastic leukemia. MDS was diagnosed in a 69-year-old man in April 2007. Twelve month later, he developed T-acute lymphoblastic leukemia. The blasts were positive for expression of CD2, CD3, CD5, CD7, CD45, and HLA-DR, leading to a diagnosis of T-lymphoblastic leukemia. The patient was treated with chemotherapy, but he died of multiple organ failure. CONCLUSION: The mechanism of lymphoid transformation is not yet fully understood. This case clinically supports the nature of MDS as a pluripotent hematopoietic stem cell disorder. MDS often transforms into acute leukemia, usually of a myeloid phenotype. The transformation of MDS into acute lymphoblastic leukemia is extremely rare.

Effect of platelet count on secretion capacity: formulization and use of the formulae for evaluation of platelet secretion in thrombocytopenic patients.

The correlation between platelet count and bleeding time is nonlinear. The bleeding time prolongs more prominently as platelet count decreases toward 10 000 microl(-1); however, it becomes stable near 100 000 microl(-1). Clinical observations suggest that platelet functional capacity may also play a role in bleeding complications during thrombocytopenia. However, no routine method has been described for evaluation of platelet function during thrombocytopenia. To test if platelet functional capacity is affected by the cell count, as suggested by the platelet count-bleeding time correlation. To evaluate lumiaggregometry as a possible tool for studying platelet functions and prediction of bleeding in thrombocytopenic patients. Collagen-induced ATP release was studied in different dilutions of 22 healthy platelet-rich plasmas. The relationship between platelet count and ATP release was formulized. ATP release was also tested in 24 thrombocytopenic (10 000-50 000 microl(-1). ) patients, and the results were compared with expected levels derived from the formulae. ATP release increased in a cubic fashion as platelet count elevated. ATP secretion values were within normal limits or increased in patients with idiopathic thrombocytopenic purpura. However, some patients with megakaryocyte deficiency had a secretion defect. ATP secretion was decreased in four out of seven patients with bleeding symptoms compared with no persons without bleeding (P = 0.003). Platelet functional capacity is affected by the cell count. Lumiaggregometry is potentially useful in evaluating platelet functions during thrombocytopenia.

Soluble platelet glycoprotein V in distinct disease states of pathological thrombopoiesis.

Quantitative platelet disorders (i.e., thrombocytosis or thrombocytopenia) may also be associated with qualitative platelet alterations. Clonal thrombocythemia (CT), reactive thrombocytosis (RT), immune thrombocytopenic purpura (ITP), and thrombocytopenia of aplastic pancytopenia (AA) or infiltrative bone marrow disorders represent the major classes of pathological thrombopoiesis. Glycoprotein V may serve as an in vivo marker of platelet activation in thrombotic and hemorrhagic states. The aim of this study was to assess circulating plasma soluble platelet glycoprotein V (sGPV) concentrations in distinct disease states of pathological thrombopoiesis. The whole study group comprised 20 patients with thrombocytopenia, 32 patients with thrombocytosis and 14 healthy adults as the control group. sGPV was significantly increased in the group of thrombocytosis patients in comparison to the thrombocytopenic group and the healthy control groups. When sGPV levels were corrected according to platelet number (sGPV/tr), this ratio was very high in patients with thrombocytopenia compared to patients with thrombocytosis and the control group. Our results suggest that there is an ongoing platelet activation associated with thrombocytosis regardless of its origin is either CT or RT. Therefore, glycoprotein V system may serve to activate residual platelets in thrombocytopenia regardless of its origin is either ITP or AA.

Angiotensin-converting enzyme expression of the lymphoma-associated macrophages in the lymph nodes of Hodgkin's disease.

OBJECTIVE: Angiotensin-converting enzyme (ACE) is involved in the control of cellular proliferation. Tumor-associated macrophages promote lymphoma pathogenesis via affecting tumor cell growth and associated survival factors. We assessed ACE expression in the neoplastic lymph node microenvironment of Hodgkin's lymphoma (HL), particularly in macrophages and in nonneoplastic lymphoid tissue. METHODS: Paraffin sections of the lymph nodes from randomly selected 20 HL cases with nodular sclerosing and 20 mixed cellular types were included into the study. Five normal tonsils and five lymph nodes showing reactive lymphoid hyperplasia were used as controls. Immunohistochemistry of lymph node biopsies had been performed with monoclonal antibody against human ACE. Sections were evaluated by two pathologists. RESULTS: ACE-expressing histiocytes were observed in lymph nodes of HL. ACE staining was also observed in the vascular endothelium in all the tissues evaluated. Neoplastic lymphoid tissues and control tissues did not express ACE. CONCLUSION: ACE expression of the lymphoma-associated macrophages in the lymph nodes of HL may represent the point of cross-talk between renin-angiotensin system (RAS) and lymphomagenesis. ACE could serve in the pathobiological function of the tissue-based macrophages in tumorigenesis of HL.

Renin-angiotensin system expression in the K562 human erythroleukaemic cell line.

Local renin-angiotensin system (RAS) may affect leukaemic cell production within the bone marrow microenvironment. Angiotensin-converting enzyme (ACE), renin, and angiotensin could influence leukaemogenesis. In this study, mRNA expressions of the major RAS components (ACE, renin, and angiotensinogen) in K562 human erythroleukaemia cell line have been searched by Real Time quantitative polymerase chain reaction. K562 blasts are multipotential, haematopoietic malignant cells that spontaneously differentiate into recognisable progenitors of the erythrocyte, granulocyte and monocytic series. We observed significant expressions of ACE, renin, and angiotensinogen in K562 leukaemic blast cells. Therefore, K562 human erythroleukaemia cell line may serve as an in vitro model to elucidate the role of RAS in leukaemia and to test the effects of RAS-affecting drugs on leukaemic cellular proliferation.