Clinical Leukemia最新文献_第5页

Increased Apoptosis as a Mechanism of Ineffective Erythropoiesis in Myelodysplastic Syndromes 细胞凋亡增加是骨髓增生异常综合征中无效红细胞生成的机制

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.014

Rosangela Invernizzi, Erica Travaglino

{"title":"Increased Apoptosis as a Mechanism of Ineffective Erythropoiesis in Myelodysplastic Syndromes","authors":"Rosangela Invernizzi, Erica Travaglino","doi":"10.3816/CLK.2008.n.014","DOIUrl":"10.3816/CLK.2008.n.014","url":null,"abstract":"<div><p>Ineffective hematopoiesis, with premature death of marrow myeloid precursors, is a hallmark of myelodysplastic syndromes (MDS), with the apparent paradox of peripheral cytopenia associated with hypercellular bone marrow (BM). Excessive apoptosis appears relevant especially in low-risk MDS. Apoptosis, triggered by the BM microenvironment and/or intrinsic cellular defects, is regulated at different levels by numerous factors, such as oncogenes and their protein products, hematopoietic growth factors, immunologic factors, cell-cell or cellstromal interactions, critical adhesion receptors, and various cytokines. Deregulation of both the intrinsic and the extrinsic pathways have been reported in MDS cells. Many studies provide evidence that the activation of the Fas/Fas-ligand system might represent an important pathogenetic mechanism. Recently, it has been demonstrated that the erythroid apoptosis of low-risk MDS is initiated at a very early stage of stem cells and associated with mitochondrial dysfunction. There is a constitutive triggering to apoptosis via cytochrome C release from the mitochondrial intermembrane space, with subsequent activation of effector caspases and increased sensitivity to death ligands triggering the extrinsic apoptotic pathway. The role of the mitochondrial pathway might be relevant especially in refractory anemia with ring sideroblasts, where abnormalities in mitochondrial ferritin expression might directly influence iron homeostasis and contribute to alter the balance between cell growth and death. The pathogenesis of refractory anemia without ring sideroblasts seems to be more heterogeneous, with the involvement of alternative mechanisms, including T-cell–mediated BM failure. Elucidation of these pathogenetic mechanisms might lead to the development of novel therapeutic strategies.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 2","pages":"Pages 113-120"},"PeriodicalIF":0.0,"publicationDate":"2008-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83842409","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}

引用次数: 6

Imatinib Compared with Imatinib/Cytarabine for the First-Line Treatment of Early Philadelphia Chromosome–Positive Chronic Myeloid Leukemia: Results of a Randomized Clinical Trial of the Mexican Collaborative Leukemia Group 伊马替尼与伊马替尼/阿糖胞苷一线治疗早期费城染色体阳性慢性髓性白血病的比较:墨西哥协作白血病组的随机临床试验结果

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.016

Rafael Hurtado-Monroy , Pablo Vargas-Viveros , Myrna Candelaria , Eduardo Cervera , Judith Cruz , Olga Gutierrez , Juan Labardini

{"title":"Imatinib Compared with Imatinib/Cytarabine for the First-Line Treatment of Early Philadelphia Chromosome–Positive Chronic Myeloid Leukemia: Results of a Randomized Clinical Trial of the Mexican Collaborative Leukemia Group","authors":"Rafael Hurtado-Monroy , Pablo Vargas-Viveros , Myrna Candelaria , Eduardo Cervera , Judith Cruz , Olga Gutierrez , Juan Labardini","doi":"10.3816/CLK.2008.n.016","DOIUrl":"10.3816/CLK.2008.n.016","url":null,"abstract":"<div><h3>Background</h3><p>In an attempt to improve the cytogenetic and molecular response rate in Philadelphia chromosome–positive early chronic-phase CML, we compared the combination of imatinib plus low-dose cytarabine (Ara-C) versus imatinib alone.</p></div><div><h3>Patients and Methods</h3><p>After a follow-up of 4 years, we included 112 patients in a randomized allocation to receive imatinib 400 mg alone orally every day (group A, 81 patients) versus imatinib in the same schedule plus Ara-C 10 mg/m<sup>2</sup> per day by subcutaneous injection daily every 10 days each month (group B, 31 patients). Both treatment groups were comparable according to hematologic basal parameters, age, sex, and previous treatment.</p></div><div><h3>Results</h3><p>Complete hematologic response was achieved in > 90% of patients in both groups; however, a shorter time and a higher complete cytogenetic response rate was documented in patients in group B compared with patients treated with imatinib alone (48.5% vs. 34%). Although a higher relapse-free survival (RFS) was documented in group B, no difference was observed in overall survival (OS) in both groups.</p></div><div><h3>Conclusion</h3><p>Our results show that the addition of Ara-C in the treatment of patients with chronic-phase CML clearly improved the cytogenetic response rate and the RFS, but new modalities of treatment need to be evaluated after relapse because the OS rate was similar in both groups. Of interest is that there was more progression in group A than in group B (16 cases vs. 1 case). This modality of therapy needs to be compared with new emerging options of first-line treatment in this disease.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 2","pages":"Pages 128-132"},"PeriodicalIF":0.0,"publicationDate":"2008-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80578087","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}

引用次数: 5

Arsenic Trioxide and Acute Promyelocytic Leukemia: A Drug for All Stages of Disease 三氧化二砷和急性早幼粒细胞白血病:一种治疗所有阶段疾病的药物

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.013

Kamran Alimoghaddam

引用次数: 1

Proposals for a Grading System for Diagnostic Accuracy of Myelodysplastic Syndromes 骨髓增生异常综合征诊断准确性分级系统的建议

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.012

Akira Matsuda , Itsuro Jinnai , Yasushi Miyazaki , Masao Tomonaga

{"title":"Proposals for a Grading System for Diagnostic Accuracy of Myelodysplastic Syndromes","authors":"Akira Matsuda , Itsuro Jinnai , Yasushi Miyazaki , Masao Tomonaga","doi":"10.3816/CLK.2008.n.012","DOIUrl":"10.3816/CLK.2008.n.012","url":null,"abstract":"<div><p>Despite recent advances in cytogenetics and molecular research, universal biomarkers for the diagnosis of the myelodysplastic syndromes (MDS) are still lacking. It is not easy to diagnose MDS by morphology alone, particularly in patients with < 5% blasts in the bone marrow (BM) and normal karyotype. Therefore, the possibility of misdiagnosis and discordance among observers can occur. In order to resolve these problems, we propose a grading system for diagnostic accuracy of MDS. The diagnostic accuracy of MDS is graded into “definite,” “probable,” or “possible” in addition to “idiopathic cytopenia(s) of uncertain significance (ICUS).” The criteria of grading for diagnostic accuracy are a combination of (1) the frequency of blasts in BM, (2) grade of dysplasia (high, intermediate, or low), and (3) division of cytogenetics (abnormal, normal, or unknown). For quantitative morphologic evaluation of dysplasias, we classified morphologic dysplastic changes into highly specific category A (pseudo–Pelger-Huet anomaly, degranulation of neutrophils, micromegakaryocytes, and ringed sideroblasts) and less specific category B (dysplasias other than those in category A). We believe that diagnostic problems would be reduced by using our grading system and repeating BM examination at suitable intervals for patients who are allocated into the “possible” or “ICUS” categories, and this will make the vague margin of MDS category clearer.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 2","pages":"Pages 102-106"},"PeriodicalIF":0.0,"publicationDate":"2008-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86266924","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}

引用次数: 9

Highlights from the 49th Annual Meeting of the American Society of Hematology: Atlanta, GA; December 8–11, 2007 第49届美国血液学学会年会:亚特兰大，GA;2007年12月8日至11日

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.1016/S1931-6925(12)60048-5

Marissa Shrader PhD, Jorge E. Cortés MD

引用次数: 0

First-Line Treatment in Chronic Lymphocytic Leukemia: A Risk-Stratified Approach 慢性淋巴细胞白血病的一线治疗:风险分层方法

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.015

Chadi Nabhan

引用次数: 0

Rituximab Can Induce a Durable Response in Refractory Immune Thrombocytopenic Purpura Associated with Chronic Lymphocytic Leukemia: Case Report and Review of the Literature 利妥昔单抗治疗难治性免疫性血小板减少性紫癜伴慢性淋巴细胞白血病:病例报告及文献回顾

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.018

Thein H. Oo

引用次数: 0

Implications of MicroRNAs in Normal Hematopoiesis and Human Leukemia microrna在正常造血和人类白血病中的意义

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.011

Muller Fabbri , Ramiro Garzon

引用次数: 0

What We Don't Know About Resistance to Tyrosine Kinase Inhibitors in CML: What Makes CML Cells a Tougher Enemy Than Expected? 我们所不知道的CML对酪氨酸激酶抑制剂的耐药性:是什么使CML细胞比预期的更强大?

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.010

Giovanni Martinelli, Simona Soverini, Ilaria Iacobucci

引用次数: 2

Chronic Myeloid Leukemia: Origin, Development, Response to Therapy, and Relapse 慢性髓性白血病:起源、发展、治疗反应和复发

Clinical Leukemia Pub Date : 2008-05-01 DOI: 10.3816/CLK.2008.n.017

David Dingli , Arne Traulsen , Jorge M. Pacheco

{"title":"Chronic Myeloid Leukemia: Origin, Development, Response to Therapy, and Relapse","authors":"David Dingli , Arne Traulsen , Jorge M. Pacheco","doi":"10.3816/CLK.2008.n.017","DOIUrl":"10.3816/CLK.2008.n.017","url":null,"abstract":"<div><h3>Background</h3><p>The introduction of imatinib, the first of a family of abl kinase inhibitors, opened a new era in the therapy of chronic myeloid leukemia (CML). The majority of treated patients achieve complete cytogenetic response, although the disease is often detectable by molecular techniques.</p></div><div><h3>Materials and Methods</h3><p>Using a mathematical model for the architecture of hematopoiesis and progression of disease as well as clinical data, we develop a unified framework that models the origin and clonal expansion of CML, the response to abl kinase inhibitors, and relapse upon cessation of therapy.</p></div><div><h3>Results</h3><p>The model predicts that a small pool of mutated stem cells is enough to drive CML. Inhibition of the abl kinase decreases the self-renewal capability of CML progenitors, altering their fitness compared with normal progenitors. Persistence of CML progenitors, however, is responsible for the rapid relapses observed upon cessation of therapy. We demonstrate how the architecture of hematopoiesis plays an instrumental role in growth of the CML clone and its response to treatment.</p></div><div><h3>Conclusion</h3><p>A small pool of stem cells is enough to drive the chronic phase of CML. Imatinib reverses the fitness advantage of CML cells, allowing return of normal hematopoiesis in most patients. Persistence of CML progenitor cells seems to be responsible for the observed relapse kinetics.</p></div>","PeriodicalId":100271,"journal":{"name":"Clinical Leukemia","volume":"2 2","pages":"Pages 133-139"},"PeriodicalIF":0.0,"publicationDate":"2008-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLK.2008.n.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90343282","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}

引用次数: 33