Clinical Leukemia最新文献

{"title":"Concurrent Activation of c-MYC and Bcl-6 by Translocation of Both Oncogenes to the Same Immunoglobulin Heavy Chain Locus","authors":"A. Zámečníkova, S. A. Bahar, R. Pandita","doi":"10.3816/CLK.2008.N.009","DOIUrl":"https://doi.org/10.3816/CLK.2008.N.009","url":null,"abstract":"Abstract Concurrent occurrence of 2 specific chromosome translocations is a relatively rare phenomenon and only occasionally has been described in hematologic malignancies. Individual cases concurrently harboring c-MYC/immunoglobulin (Ig)H and Bcl-6/IgH rearrangements have been previously reported in B-cell malignancies; however, the occurrence of 3-way translocations simultaneously affecting 3 key genes involved in the pathogenesis was described only in individual cases. This report describes a patient diagnosed with acute lymphoblastic leukemia with genetic alterations concurrently affecting the c-MYC, Bcl-6, and IgH loci in addition to the rearrangement of the long arm of chromosome 1. Our case might be of interest because of the: (1) concurrent translocations of Bcl-6 and c-MYC oncogenes to the same IgH loci as a result of a 3-way recombination; (2) disruption of the bcl-6 gene because of the cryptic insertion of IgH in 3q27; (3) presence of jumping translocation affecting the long arm of chromosome 1; and (4) further illustration of the utility of fluorescence in situ hybridization studies in the identification of cryptic and complex translocations in routine diagnosis. Concurrent translocations of 2 key oncogenes to the same immunoglobulin loci demonstrate novel features of instability of bcl-6 and IgH genes and might present a novel mechanism of gene activation in B-cell malignancies.","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"47 1","pages":"68-71"},"PeriodicalIF":0.0,"publicationDate":"2008-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89803567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent Activation of c-MYC and Bcl-6 by Translocation of Both Oncogenes to the Same Immunoglobulin Heavy Chain Locus","authors":"Adriana Zámečníkova ,&nbsp;Soad Al Bahar ,&nbsp;Ramesh Pandita","doi":"10.3816/CLK.2008.n.009","DOIUrl":"https://doi.org/10.3816/CLK.2008.n.009","url":null,"abstract":"<div><p>Concurrent occurrence of 2 specific chromosome translocations is a relatively rare phenomenon and only occasionally has been described in hematologic malignancies. Individual cases concurrently harboring c-MYC/immunoglobulin (Ig)H and Bcl-6/IgH rearrangements have been previously reported in B-cell malignancies; however, the occurrence of 3-way translocations simultaneously affecting 3 key genes involved in the pathogenesis was described only in individual cases. This report describes a patient diagnosed with acute lymphoblastic leukemia with genetic alterations concurrently affecting the c-MYC, Bcl-6, and IgH loci in addition to the rearrangement of the long arm of chromosome 1. Our case might be of interest because of the: (1) concurrent translocations of Bcl-6 and c-MYC oncogenes to the same IgH loci as a result of a 3-way recombination; (2) disruption of the <em>bcl-6</em> gene because of the cryptic insertion of IgH in 3q27; (3) presence of jumping translocation affecting the long arm of chromosome 1; and (4) further illustration of the utility of fluorescence in situ hybridization studies in the identification of cryptic and complex translocations in routine diagnosis. Concurrent translocations of 2 key oncogenes to the same immunoglobulin loci demonstrate novel features of instability of <em>bcl-6</em> and <em>IgH</em> genes and might present a novel mechanism of gene activation in B-cell malignancies.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 1","pages":"Pages 68-71"},"PeriodicalIF":0.0,"publicationDate":"2008-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91680367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Treatment Strategies Improving Outcomes in Patients with Myelodysplastic Syndromes with the Deletion 5q Abnormality","authors":"Mikkael A. Sekeres ,&nbsp;Alan F. List","doi":"10.3816/CLK.2008.n.003","DOIUrl":"10.3816/CLK.2008.n.003","url":null,"abstract":"<div><p>Myelodysplastic syndromes (MDS) have undergone a therapeutic revolution in the past decade that has redefined treatment strategies for this disease. Patients with early-stage MDS who harbor a clonal chromosome 5q deletion (del[5q]) represent a distinct subset of MDS that is clinically, pathologically, and often prognostically distinct. While the vast majority of patients with MDS are red blood cell transfusion dependent, natural history of the disease varies from indolent (with a low-risk of leukemia evolution), in patients with isolated del(5q), to a high-risk of leukemia and poor survival in patients with a complex karyotype. Lenalidomide, which specifically targets the del(5q) clone, selectively suppresses the clone to yield transfusion independence and a cytogenetic response in approximately two thirds of patients, a response that is sustained for a median of 2.2 years. Features associated with a higher likelihood of transfusion independence include early treatment-related cytopenias and lower baseline transfusion needs, whereas the expectation for extended overall survival and freedom from leukemia evolution is greatest in cytogenetic responders. Future applications of lenalidomide will target patients with del(5q) with more advanced disease, will exploit the potentiation effects of lenalidomide's interaction with other agents, and will target novel pathways.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 1","pages":"Pages 28-33"},"PeriodicalIF":0.0,"publicationDate":"2008-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83339158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Venous Thrombosis in Patients with Polycythemia Vera and Essential Thrombocythemia","authors":"V. Stefano, T. Za, E. Rossi, E. Elli, A. Vannucchi, M. Ruggeri, C. Micò, N. Vianelli, R. Cacciola, A. Tieghi, C. Santoro, E. Pogliani, P. Guglielmelli, L. Pieri, F. Scognamiglio, F. Rodeghiero, G. Finazzi, L. Gugliotta, G. Leone, T. Barbui","doi":"10.3816/CLK.2007.N.027","DOIUrl":"https://doi.org/10.3816/CLK.2007.N.027","url":null,"abstract":"Abstract Purpose The risk of recurrent venous thromboembolism (VTE) in patients with polycythemia vera and essential thrombocythemia has been scarcely addressed, and whether long-term oral anticoagulant treatment or acetylsalicylic acid should be recommended after first occurrence of deep venous thrombosis (DVT) is unknown. This multicenter cohort study was aimed to assess the rate of recurrent VTE in patients with polycythemia vera or essential thrombocythemia in comparison with a control group of individuals with previous VTE and without neoplastic diseases. Patients and Methods We retrospectively estimated the rate of recurrence in 79 patients with myeloproliferative disorders (MPDs; polycythemia vera/essential thrombocythemia, 45/34) and with a previous proximal DVT. Patients were divided into 2 groups. The first comprised 41 patients who received acetylsalicylic acid after 6 months of oral anticoagulant treatment. The second group was composed of 38 patients given long-term oral anticoagulant treatment without acetylsalicylic acid. The majority of patients were treated with cytotoxic drugs. The results were compared with the recurrences seen in 176 patients without cancer with previous proximal DVT given short-term oral anticoagulant treatment. Results In the patients with polycythemia vera and essential thrombocythemia, the rate of recurrent DVT was higher in the group receiving acetylsalicylic acid (32%) compared with the group on oral anticoagulant treatment (16%), although not statistically significant. The rate of recurrent DVT in MPD cases receiving acetylsalicylic acid was quite similar to that of patients without cancer (33%). The cumulative probability of recurrent VTE indicated a trend of fewer events in the MPD cases on long-term oral anticoagulant treatment. In the patients with MPDs, the incidence of major bleeding during oral anticoagulant treatment or acetylsalicylic acid was 1% and 0.5% patient-years (years of observation), respectively. Conclusion This retrospective analysis would suggest a long-term oral anticoagulant treatment after a first DVT in patients with polycythemia vera and essential thrombocythemia. However, this indication should be weighed against the risk of major hemorrhagic events that seems lower during long-term prophylaxis with acetylsalicylic acid. Therefore, a prospective clinical trial comparing acetylsalicylic acid in patients with polycythemia vera and essential thrombocythemia with oral anticoagulant treatment in the prevention of recurrent VTE is warranted.","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"30 1","pages":"339-344"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85474044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scrotal Edema Associated with the Use of Dasatinib in Patients with Chronic Myeloid Leukemia","authors":"Nitin Jain ,&nbsp;Hagop Kantarjian ,&nbsp;Pat Ault ,&nbsp;Jorge Cortés","doi":"10.3816/CLK.2007.n.030","DOIUrl":"10.3816/CLK.2007.n.030","url":null,"abstract":"<div><p>Dasatinib is a new tyrosine kinase inhibitor which is approved by the FDA for the treatment of patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. Dasatinib can cause fluid retention in some patients, leading to peripheral edema and pleural effusion. Herein, we report 2 patients with chronic phase CML who developed significant scrotal and penile edema while on treatment with dasatinib. In both patients, transient dasatinib interruption and use of diuretics helped alleviate the symptoms. Both patients had the dose schedule of dasatinib switched to once daily from twice daily. Scrotal and penile edemas are unusual manifestations of fluid retention that, to our knowledge, have not been reported in patients treated with dasatinib. Recognition of these symptoms as a potential complication of dasatinib will help prevent unnecessary investigations, facilitate adequate management, and help alleviate patient anxiety.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"1 6","pages":"Pages 357-358"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2007.n.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83165003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soul Searching in Myelodysplastic Syndromes","authors":"G. Garcia-Manero","doi":"10.3816/CLK.2007.N.024","DOIUrl":"https://doi.org/10.3816/CLK.2007.N.024","url":null,"abstract":"","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"13 1","pages":"319"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88766243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soul Searching in Myelodysplastic Syndromes","authors":"Guillermo Garcia-Manero MD (Associate Professor)","doi":"10.3816/CLK.2007.n.024","DOIUrl":"https://doi.org/10.3816/CLK.2007.n.024","url":null,"abstract":"","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"1 6","pages":"Page 319"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2007.n.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91774484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growing evidence for an underestimation of poor-risk cytogenetics in the international prognostic scoring system in myelodysplastic syndromes","authors":"C. Steidl, J. Schanz, M. Pfeilstöcker, T. Nösslinger, B. Hildebrandt, A. Kuendgen, M. Lübbert, R. Kunzmann, A. Giagounidis, C. Aul, L. Trümper, O. Krieger, R. Stauder, T. Müller, F. Wimazal, P. Valent, C. Fonatsch, U. Germing, D. Haase","doi":"10.3816/CLK.2007.N.029","DOIUrl":"https://doi.org/10.3816/CLK.2007.N.029","url":null,"abstract":"Abstract The International Prognostic Scoring System (IPSS) for myelodysplastic syndromes (MDS) identifies bone marrow (BM) blasts, cytogenetics, and the number of cytopenias as major variables with impact on disease outcome. Weighting of these variables defines distinct subgroups using multivariate analysis approaches. Recent studies, including the work of our group, indicate an underestimation of unfavorable cytogenetics in the IPSS. To delineate the prognostic impact of poor-risk karyotypes in relation to blast counts, we studied clinical outcome of cytogenetic and blast count subgroups in a large cohort of 1440 patients with MDS. Using univariate analytic tools, median survival times of 158 patients with poor-risk cytogenetics and 66 patients with blast counts of > 20% were 11.1 months and 9 months, respectively. Median survival times of patients with poor-risk cytogenetics and normal blast counts (n = 60; median survival, 17 months) were not significantly different from those of good-risk karyotypes and highly elevated BM blasts (11%–20%: n = 89; median survival, 22 months; P = .098; > 20%: n = 32; median survival, 13 months; P = .892). Our data indicate an equal prognostic significance of poor-risk cytogenetics compared with highly elevated BM blasts and suggest a higher score for unfavorable karyotypes in future integrative prognostic systems in MDS.","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"20 1","pages":"353-356"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78507180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmasking of Chronic Myelomonocytic Leukemia after Treatment of Chronic Lymphocytic Leukemia with Rituximab","authors":"Lesley N. Bobek ,&nbsp;Jason K. Hyde ,&nbsp;Keith S. Hansen","doi":"10.3816/CLK.2007.n.031","DOIUrl":"10.3816/CLK.2007.n.031","url":null,"abstract":"<div><p>The association of myelodysplastic syndromes with lymphoid malignancies has rarely been reported. To our knowledge, there are only 5 reported cases of chronic lymphocytic leukemia (CLL) and chronic myelomonocytic leukemia (CMML) occurring in the same patient. Herein, we describe the case of an 80-year-old woman diagnosed with CLL. She declined chemotherapy and began weekly rituximab 375 mg/m² intravenously. She initially had a solid partial response to treatment. However, after 2 treatments with rituximab her white blood cell count increased, and a peripheral smear was remarkable for large, cleaved, folded cells, identified as monocytes. The previous bone marrow biopsy was retrieved and restained with an α-naphthol butyl esterase for monocytes. An increased atypical monocytic population was exposed, indicative of an evolving CMML. Her 2 malignancies probably arose from 2 different clones by chance. Treatment was begun with decitabine, but with no response. The patient remains transfusion dependent although relatively asymptomatic on hydroxyurea.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"1 6","pages":"Pages 359-362"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2007.n.031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83264084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growing Evidence for an Underestimation of Poor-Risk Cytogenetics in the International Prognostic Scoring System in Myelodysplastic Syndromes","authors":"Christian Steidl ,&nbsp;Julie Schanz ,&nbsp;Michael Pfeilstöcker ,&nbsp;Thomas Nösslinger ,&nbsp;Barbara Hildebrandt ,&nbsp;Andrea Kuendgen ,&nbsp;Michael Lübbert ,&nbsp;Regina Kunzmann ,&nbsp;Aristoteles Giagounidis ,&nbsp;Carlo Aul ,&nbsp;Lorenz Trümper ,&nbsp;Otto Krieger ,&nbsp;Reinhard Stauder ,&nbsp;Thomas H. Müller ,&nbsp;Friedrich Wimazal ,&nbsp;Peter Valent ,&nbsp;Christa Fonatsch ,&nbsp;Ulrich Germing ,&nbsp;Detlef Haase","doi":"10.3816/CLK.2007.n.029","DOIUrl":"https://doi.org/10.3816/CLK.2007.n.029","url":null,"abstract":"<div><p>The International Prognostic Scoring System (IPSS) for myelodysplastic syndromes (MDS) identifies bone marrow (BM) blasts, cytogenetics, and the number of cytopenias as major variables with impact on disease outcome. Weighting of these variables defines distinct subgroups using multivariate analysis approaches. Recent studies, including the work of our group, indicate an underestimation of unfavorable cytogenetics in the IPSS. To delineate the prognostic impact of poor-risk karyotypes in relation to blast counts, we studied clinical outcome of cytogenetic and blast count subgroups in a large cohort of 1440 patients with MDS. Using univariate analytic tools, median survival times of 158 patients with poor-risk cytogenetics and 66 patients with blast counts of &gt; 20% were 11.1 months and 9 months, respectively. Median survival times of patients with poor-risk cytogenetics and normal blast counts (n = 60; median survival, 17 months) were not significantly different from those of good-risk karyotypes and highly elevated BM blasts (11%–20%: n = 89; median survival, 22 months; <em>P</em> = .098; &gt; 20%: n = 32; median survival, 13 months; <em>P</em> = .892). Our data indicate an equal prognostic significance of poor-risk cytogenetics compared with highly elevated BM blasts and suggest a higher score for unfavorable karyotypes in future integrative prognostic systems in MDS.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"1 6","pages":"Pages 353-356"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2007.n.029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91774485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}