共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Foà R 《Haematologica》2005,90(4):434-435
3.
The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes 下载免费PDF全文
Src family kinases (SFKs) were described to be overexpressed in chronic lymphocytic leukemia (CLL). We wished to examine the effects of the Src and Abl kinase inhibitor dasatinib on the intracellular signaling and survival of CLL cells. Dasa-tinib showed a dose- and time-dependent reduction of global tyrosine phosphorylation and of activating phosphotyrosine levels of SFKs. Treatment with 100 nM dasatinib led to decreased levels of the activated, phosphorylated forms of Akt, Erk1/2, and p38, and induced PARP cleavage through caspase activity. In Mec1 and JVM-3 cell lines, dasatinib increased p53 protein levels and inhibited proliferation. In freshly isolated CLL cells, dasatinib reduced the expression of Mcl-1 and Bcl-x(L). Combination of 5 microM dasatinib and fludarabine increased the apoptosis induction of each by approximately 50%. In 15 primary CLL samples, cells with unmutated immunoglobulin variable heavy chain (IgV(H)) genes were more sensitive to dasatinib than those with mutated IgV(H) genes (P = .002). In summary, dasatinib shows potent inhibitory effects on the survival of CLL cells in vitro, most prominently in samples obtained from patients with unfavorable prognostic features. 相似文献
4.
5.
Carlo Visco Wilma Barcellini Francesco Maura Antonino Neri Agostino Cortelezzi Francesco Rodeghiero 《American journal of hematology》2014,89(11):1055-1062
Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary. Am. J. Hematol. 89:1055–1062, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
6.
Rossi D De Paoli L Rossi FM Cerri M Deambrogi C Rasi S Zucchetto A Capello D Gattei V Gaidano G 《British journal of haematology》2008,141(5):734-736
Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case‐control study of 111 ischemic stroke patients and 119 controls, significantly higher FgEDP levels were observed in cases than in controls, both in the acute phase and in the convalescent phase. Results were only slightly affected by adjustment for cardiovascular risk factors, C‐reactive protein and fibrinogen. Our findings suggest that FgEDP might be involved in the pathogenesis of stroke. 相似文献
7.
Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia 总被引:8,自引:3,他引:8 下载免费PDF全文
Mayr C Speicher MR Kofler DM Buhmann R Strehl J Busch R Hallek M Wendtner CM 《Blood》2006,107(2):742-751
In chronic lymphocytic leukemia (CLL), chromosomes usually evade detailed cytogenetic analyses because cells poorly respond to the traditionally used set of mitogens. We applied novel technologies, such as stimulation of CLL cells either with CD40 ligand or with a combination of CpG-oligodeoxynucleotides and IL-2, to increase the frequency of metaphase spreads for detailed chromosome analysis in 96 patients with CLL. This approach revealed that translocations occurred in 33 of 96 (34%) of our patients with CLL. The presence of translocations defined a new prognostic subgroup because these patients have significantly shorter median treatment-free survival (24 months vs 106 months; P < .001) and significantly inferior overall survival (OS; median, 94 months) than patients without translocations (346 months; P < .001). In multivariate analysis-including Binet stage, complex karyotype, CD38 expression, and 17p deletions-translocation proved to be the prognostic marker with the highest impact for an unfavorable clinical outcome (P < .001). In summary, we identified a new subgroup of patients with CLL defined by chromosomal trans-locations and poor prognosis. Our data may facilitate the identification of molecular events crucial for transforming activity in this disease and should have implications for risk-adapted clinical management of patients with CLL. 相似文献
8.
Chronic lymphocytic leukemia (CLL), the most common form of leukemia in Western countries, rarely induces glomerular disease, but membranoproliferative glomerulonephritis or immunotactoid glomerulopathy has been reported. The proliferating cells in CLL are of mature B-cell origin and produce monoclonal immunoglobulin (Ig), thus leading to various kinds of autoimmune disorders or immunotactoid glomerulopathy. Although there have been a few reported cases of amyloidosis accompanying CLL, the type of amyloid fibrils has not been demonstrated nor described in detail, particularly regarding monoclonal Ig productivity. We report a rare case of amyloidosis associated with CLL, in which we detected κ-light chain type monoclonal Ig in the sera, urine, and on the surface membrane of lymphocytes, and discuss an association between monoclonal Ig-related disease and non-Hodgkin's lymphoma. 相似文献
9.
Elter T Vehreschild JJ Gribben J Cornely OA Engert A Hallek M 《Annals of hematology》2009,88(2):121-132
Infection is a significant cause of morbidity and death in patients with chronic lymphocytic leukemia (CLL). Increased infectious
events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient’s immune
system over the course of disease. The humanized, anti-CD52 monoclonal antibody alemtuzumab (Campath or Campath-1H) has shown
notable activity for both untreated and fludarabine-refractory CLL. The antibody not only targets malignant cells but also
affects normal, healthy immune cells. The cumulative effects of the malignancy and successive courses of treatments adversely
impinge on a patient’s defense response to certain bacterial, fungal, and viral infections. In this review article, we provide
an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively
monitoring and managing infections in CLL patients. 相似文献
10.
11.
A patient with chronic lymphocytic leukemia (CLL) is described in whom hypercalcemia occurred in association with elevation of the peripheral lymphocyte count and expansion of total tumor mass. Hypercalcemia was ameliorated with the institution of chemotherapy for the leukemic process and subsequent fall in WBC count and decrease in total tumor burden; hypercalcemia recurred with relapse of the leukemic process. The serum immunoreactive parathyroid hormone (iPTH) concentration, when measured, was inappropriately elevated for the degree of hypercalcemia. The hypercalcemia would appear to be a direct consequence of the leukemia, and possibly involved secretion of a parathyroid hormone-like polypeptide by the CLL cells. Although a possible role for either an osteoclast-activating substance or prostaglandins was not excluded, they would not account for the elevated serum iPTH levels observed. 相似文献
12.
Gerald Y Minuk Betty Lerner Spencer B Gibson James B Johnston Julia Uhanova Anton Andonov Jun Wu 《Journal canadien de gastroenterologie》2014,28(3):131-134
BACKGROUND:
Whether chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections contribute to the pathogenesis and/or course of chronic lymphocytic leukemia is unclear.OBJECTIVE:
To document the prevalences of HBV and HCV infections in chronic lymphocytic leukemia patients, and to determine whether infected patients experience more aggressive disease than those without infection.METHODS:
Patient sera were screened for antibodies to HBV core antigen and HCV (anti-HCV) using ELISA; both sera and peripheral blood lymphocytes were further tested (regardless of antibody results) for HBV-DNA and HCV-RNA using real-time polymerase chain reaction. Prognostic markers for chronic lymphocytic leukemia included Rai stage, IgVH mutational status, β2-microglobulin levels, Zap-70 and CD38 status.RESULTS:
Fourteen of 222 (6.3%) chronic lymphocytic leukemia patients and two of 72 (2.8%) healthy controls tested positive for previous or ongoing HBV infection (OR 2.4 [95% CI 0.5 to 7.7]; P=0.25) while four of 222 (1.8%) chronic lymphocytic leukemia patients and one of 72 (1.4%) controls tested positive for HCV markers (OR 1.3 [95% CI 0.2 to 6.4]; P=0.81). The levels and distribution of the various indicators of aggressive chronic lymphocytic leukemia disease were similar among HBV- and HCV-infected and uninfected patients. Survival times were also similar. Occult HBV and HCV infection (HBV-DNA or HCV-RNA positive in the absence of diagnostic serological markers) were uncommon in chronic lymphocytic leukemia patients (0.5% and 1.8%, respectively).CONCLUSIONS:
The results of the present study do not support the hypothesis that HBV or HCV infections play an important role in the pathogenesis or course of chronic lymphocytic leukemia. 相似文献13.
14.
Amyloidosis associated with chronic lymphocytic leukemia. 总被引:2,自引:0,他引:2
Ryota Ikee Shuzo Kobayashi Noriaki Hemmi Shigenobu Suzuki Soichiro Miura 《Amyloid》2005,12(2):131-134
Chronic lymphocytic leukemia (CLL), the most common form of leukemia in Western countries, rarely induces glomerular disease, but membranoproliferative glomerulonephritis or immunotactoid glomerulopathy has been reported. The proliferating cells in CLL are of mature B-cell origin and produce monoclonal immunoglobulin (Ig), thus leading to various kinds of autoimmune disorders or immunotactoid glomerulopathy. Although there have been a few reported cases of amyloidosis accompanying CLL, the type of amyloid fibrils has not been demonstrated nor described in detail, particularly regarding monoclonal Ig productivity. We report a rare case of amyloidosis associated with CLL, in which we detected ?-light chain type monoclonal Ig in the sera, urine, and on the surface membrane of lymphocytes, and discuss an association between monoclonal Ig-related disease and non-Hodgkin's lymphoma. 相似文献
15.
Kyo K Sameshima S Tanaka Y Murayama K Shimano S Kojima M Sugihara S Sawada T 《Journal of gastroenterology》2004,39(5):479-483
It has been reported that chronic lymphocytic leukemia (CLL) often occurs concomitantly with other malignant neoplasms. However, because CLL is rare in Japan, there are only a limited number of reports of the occurrence of malignant neoplasia in Japanese patients with CLL. We report here the simultaneous occurrence of rectal cancer and CLL in a 57-year-old man. Because the clinical stage of CLL was Rai system I, we decided, in accordance with the National Cancer Institute–Sponsored Working Group guidelines, to monitor him without therapy for CLL until evidence of disease progression, and we performed abdominoperineal resection of the rectum for the cancer. The small rectal tumor was associated with aggressive lymphangiosis carcinomatosa, and multiple nodal metastases were observed in the pool of CLL cells. He died of rectal cancer 7 months after the operation, and autopsy revealed extensive metastases of the cancer. Cellular and humoral immunity is often impaired in patients with CLL, and the defective immunity in this patient may have had an etiological role in the development and rapid progression of the cancer. In the follow-up of CLL patients, we must always be aware of the possible existence of a second malignant disease. Particular attention should be paid to those with defective immunity, and screening should be performed, especially for pulmonary and gastrointestinal malignancies. 相似文献
16.
Autoimmune hyperthyroidism and thrombocytopenia developing in a patient with chronic lymphocytic leukemia 总被引:1,自引:0,他引:1
A 56-year-old white man is described whose course of chronic lymphocytic leukemia (CLL) was complicated by the occurrence of the autoimmune hyperthyroidism/thrombocytopenia syndrome. The implications of this syndrome on the treatment of CLL are discussed. 相似文献
17.
Perrot A Pionneau C Nadaud S Davi F Leblond V Jacob F Merle-Béral H Herbrecht R Béné MC Gribben JG Bahram S Vallat L 《Blood》2011,118(4):e1-15
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70(-) and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70(+) and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70(-)) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease. 相似文献
18.
19.
20.
Koski T Karhu R Visakorpi T Vilpo L Knuutila S Vilpo J 《European journal of haematology》2000,65(1):32-39
Drug resistance is a major problem in chemotherapy of chronic lymphocytic leukemia (CLL). The genetic basis and molecular pathogenesis of drug resistance in CLL remain poorly understood. Here, we have investigated the association between chromosomal aberrations and cellular resistance of CLL cells against seven drugs, gamma and ultraviolet irradiation. Samples were obtained from 35 patients having a classical form of B-CLL. Chromosomal aberrations were first analyzed by traditional karyotyping improved by using optimized mitogen combinations. DNA sequence copy number changes throughout the genome were next screened by comparative genomic hybridization. Finally, fluorescence in situ hybridization was used to detect trisomy 12 and loss of Rb and deletions at chromosome 11. The cellular sensitivity in vitro was assessed by the reduction of macromolecular protein synthesis measured as incorporation of radioactive L-leucine as an endpoint. The overall analysis disclosed a statistically highly significant difference in cellular drug resistance between patients having at least three aberrations compared with patients with fewer or no aberrations. This strongly indicates that complex rather than simple molecular mechanisms are responsible for the drug and irradiation resistance in CLL. According to published results, complex aberrations are constantly associated with poor prognosis in CLL. We demonstrated here that complex chromosomal aberrations were associated with cellular irradiation and drug resistance, which, on the other hand, may be responsible for the poor clinical outcome in CLL. 相似文献