Blood and Lymphatic Cancer-Targets and Therapy最新文献

{"title":"The Evolving Role of Brentuximab Vedotin in Classical Hodgkin Lymphoma.","authors":"Catherine Lai,&nbsp;Adrese Michael Kandahari,&nbsp;Chaitra Ujjani","doi":"10.2147/BLCTT.S231821","DOIUrl":"https://doi.org/10.2147/BLCTT.S231821","url":null,"abstract":"<p><p>The arrival of the CD30 directed antibody-drug conjugate, brentuximab vedotin (BV), has altered the approach to patients with classical Hodgkin lymphoma. Since initial approval in 2011, BV has been extensively studied in previously untreated and relapsed/refractory patients. Treatment indications for the antibody-drug conjugate have been expanded from the previously treated population to include maintenance therapy after autologous stem cell transplantation and recently, combination with chemotherapy in newly diagnosed advanced stage patients. This article will review the evolution of BV in classical Hodgkin lymphoma, detailing the studies that led to the approved indications and discussion of recent trials in combination with chemotherapy and immunotherapy.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S231821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37468005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockout Of <i>BIRC5</i> Gene By CRISPR/Cas9 Induces Apoptosis And Inhibits Cell Proliferation In Leukemic Cell Lines, HL60 And KG1.","authors":"Manizheh Narimani,&nbsp;Mohammadreza Sharifi,&nbsp;Ali Jalili","doi":"10.2147/BLCTT.S230383","DOIUrl":"https://doi.org/10.2147/BLCTT.S230383","url":null,"abstract":"<p><strong>Introduction: </strong>Human Baculoviral inhibitor of apoptosis repeat-containing 5 (<i>BIRC5</i>) which encodes survivin exhibits multiple biological activities, such as cell proliferation and apoptosis. Survivin is overexpressed in numerous malignant diseases including acute myeloid leukemia (AML). Recent studies have shown that the CRISPR/Cas9 nuclease-mediated gene-editing systems are suitable approach's for editing or knocking out various genes including oncogenes.</p><p><strong>Methods and materials: </strong>We used CRISPR-Cas9 to knockout the <i>BIRC5</i> in the human leukemic cell line, HL60, and KG1, and these cell lines were transfected with either the Cas9- and three sgRNAs expressing plasmids or negative control (scramble) using Lipofectamine 3000. The efficacy of the transfection was determined by quantitative reverse transcription-polymerase chain (RT-qPCR) and surveyor mutation assays. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively.</p><p><strong>Results: </strong>We have successfully knocked out the <i>BIRC</i>5 gene in these leukemic cells and observed that the <i>BIRC5</i>-knocked out cells by CRISPR/Cas9 showed a significant decrease (30 folds) of survivin at mRNA levels. Moreover, cell death and apoptosis were significantly induced in <i>BIRC5</i>-CRISPR/Cas9-transfected cells compared to the scramble vector.</p><p><strong>Conclusion: </strong>We demonstrated for the first time that targeting <i>BIRC5</i> by CRISPR/Cas9 technology is a suitable approach for the induction of apoptosis in leukemic cells. However, further studies targeting this gene in primary leukemic cells are required.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S230383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies For Targeting Chronic Myeloid Leukaemia Stem Cells","authors":"Giovanna Carrá, A. Cartellà, B. Maffeo, A. Morotti","doi":"10.2147/BLCTT.S228815","DOIUrl":"https://doi.org/10.2147/BLCTT.S228815","url":null,"abstract":"Abstract Chronic Myeloid Leukaemia is a myeloproliferative disorder driven by the t(9;22) chromosomal translocation coding for the chimeric protein BCR-ABL. CML treatment represents the paradigm of molecular therapy of cancer. Since the development of the tyrosine kinase inhibitor of the BCR-ABL kinase, the clinical approach to CML has dramatically changed, with a stunning improvement in the quality of life and response rates of patients. However, it remains clear that tyrosine kinase inhibitors (TKIs) are unable to target the most immature cellular component of CML, the CML stem cell. This review summarizes new insights into the mechanisms of resistance to TKIs.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82820013","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":"Prognostic analysis of CD5 expression in double-hit diffuse large B-cell lymphoma and effectiveness comparison in patients treated with dose-adjusted EPOCH plus rituximab/R-CHOP regimens","authors":"Fangwen Zhang, Ling Li, Lei Zhang, Xin Li, Xiaorui Fu, Xinhua Wang, Jingjing Wu, Zhenchang Sun, Fei Kong, L. Ren, Mingzhi Zhang","doi":"10.2147/BLCTT.S216292","DOIUrl":"https://doi.org/10.2147/BLCTT.S216292","url":null,"abstract":"Objectives To compare the efficacy of rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) with traditional rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimens in CD5+ double-hit lymphoma (DHL) and to evaluate prognostic factors. Methods We retrospectively studied 139 patients with newly diagnosed DHL/THL diffuse large B-cell lymphoma (including 20 cases CD5+ and 119 cases CD5−), 87 cases were MYC/BCL2 DHL, 30 cases were MYC/BCL6 DHL, 22 cases were THL. MYC, BCL2 and BCL6 rearrangements were examined by fluorescence in-situ hybridization. CD5 is detected by immunohistochemistry (IHC). Results The objective response rate (ORR) difference between CD5+ and CD5− was significant (80.0% vs 63.8%, P=0.003). The median follow-up time was 18 months (range: 4–39 months). Progression-free survival (PFS) of CD5+ group was significantly worse than that of CD5- (28.1% vs 59.0%, P=0.028), while no significant difference was observed in overall survival (OS) (32.1% vs 59.9%, P=0.057). Compared with the two regimens, the 2-year survival rate of DA-EPOCH-R group was significantly superior than that of R-CHOP (63.6% vs 45.4%, P=0.034 for PFS; 67.4% vs 47.8%, P=0.038 for OS). Besides, CD5+ patients receiving DA-EPOCH-R had survival benefits compared with R-CHOP in PFS (85.7% vs 23.0%, P=0.029), but there was no statistical difference in OS (87.7% vs 34.4.0%, P=0.064). However, in DA-EPOCH-R protocol, there was no significant difference between CD5+ DHL (MYC/BCl2 and MYC/BCL6) and triple-hit lymphoma (P=0.776 for PFS; P=0.728 for OS). Multivariate analysis showed that CD5+ treatment regimen and disease stage were independent prognostic factors. Conclusion Our retrospective study shows that CD5+ has a poorer prognosis than CD5− patients. Based on its improved lifetime and good tolerance on CD5+ patients, which is expected to become the first-line treatment for high-risk DLBCL types based on more clinical research.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84688760","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":"IDH1-mutated relapsed or refractory AML: current challenges and future prospects","authors":"J. Megías-Vericat, O. Ballesta-López, E. Barragán, P. Montesinos","doi":"10.2147/BLCTT.S177913","DOIUrl":"https://doi.org/10.2147/BLCTT.S177913","url":null,"abstract":"Abstract The prognosis of patients with relapsed or refractory acute myeloid leukemia (R/R AML) is discouraging with salvage standard approaches. Mutations of isocitrate dehydrogenase 1 (IDH1mut), present in 7–14% of AML patients, have been discovered recently, opening the door to targeted agents aiming to improve the outcomes in this setting. Several oral selective IDH1mut inhibitors are under investigation, ivosidenib being the first approved for R/R AML. We performed a systematic review to analyze the clinical outcomes and safety reported with IDH1mut inhibitors and other agents in adult patients with IDH1mut R/R AML. Ivosidenib in monotherapy achieved complete remission (CR) of 24%, overall response of 42%, and median overall survival of 9 months in R/R AML, and promising outcomes were reported with IDH305 and FT-2102. IDH1mut inhibitors were generally well tolerated, but some therapy-related toxicities should be monitored, including IDH-differentiation syndrome, prolongation of the QT interval, and leukocytosis, all manageable and reversible. Also, venetoclax, CB-839, PARP inhibitors, and IDH1 peptide vaccine are being studied in IDH1mut AML. The results of the ongoing and upcoming clinical trials will bring new evidence to establish the role of IDH1mut inhibitors in therapeutic strategies of AML.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73049269","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":"The expanding role of venetoclax in chronic lymphocytic leukemia and small lymphocytic lymphoma.","authors":"Michael Schieber, Shuo Ma","doi":"10.2147/BLCTT.S177009","DOIUrl":"10.2147/BLCTT.S177009","url":null,"abstract":"<p><p>The BCL-2 protein family members inhibit cellular apoptosis, and their overexpression represents a common survival adaption in cancer. Recently, a selective BCL-2 inhibitor ABT-199, venetoclax, has demonstrated remarkable activity in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), both as a single agent and in combination with anti-CD20 immunotherapies, such as rituximab. In this article, we review the development and latest clinical data that have led to the expanded approval of venetoclax with rituximab in relapsed/refractory CLL/SLL. We also discuss ongoing and future clinical trials designed to evaluate the efficacy of venetoclax in previously untreated patients and to investigate venetoclax combinations with inhibitors of B-cell receptor signaling pathway. These studies hope to offer an expanded list of chemotherapy-free regimens for patients with CLL/SLL.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2019-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/fb/blctt-9-9.PMC6859801.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37601212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for minimal residual disease detection: current perspectives","authors":"G. Andreani, D. Cilloni","doi":"10.2147/BLCTT.S172693","DOIUrl":"https://doi.org/10.2147/BLCTT.S172693","url":null,"abstract":"Abstract Currently, the post-remission treatment in acute leukemia is based on the genetic profile of leukemic cells at diagnosis (ie, FLT3 ITD positivity) and on the level of measurable residual disease (MRD) after induction and consolidation chemotherapy. Two methods are currently preferred for MRD evaluation in many centers: multiparameter flow cytometry and real-time quantitative PCR. Additional methods such as next-generation sequencing and digital PCR are under investigation, in an attempt to increase the sensitivity and thus allowing the detection of small clones. Many studies suggest that MRD positivity after chemotherapy is associated with negative prognosis, and the reappearance of MRD during follow-up allows impending relapse to be identified and consequently enables early intervention. Finally, MRD positivity before hematopoietic stem cell transplantation is predictive of the outcome. Although the significance of MRD in acute leukemia has been widely explored, the assessment of molecular MRD is not yet a routine practice. In this review, we describe the significance of MRD in different settings and the main markers and methods used for MRD detection.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80644969","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":"Plasmablastic lymphoma: current perspectives","authors":"Andrés López, P. Abrisqueta","doi":"10.2147/BLCTT.S142814","DOIUrl":"https://doi.org/10.2147/BLCTT.S142814","url":null,"abstract":"Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy with large neoplastic cells, most of them resembling plasmablasts that have a CD20-negative phenotype. Although initially described as being associated with HIV, over the years it has also been identified in patients with solid organ transplant and immunocompetent patients. Little is known about molecular basis that drives PbL, and still its diagnosis remains challenging given its rarity. However, proper recognition of its clinical characteristics, localization, and morphological features can establish a correct diagnosis of PbL within the spectrum of CD20-negative large B-cell lymphomas (LBCLs). PbL is characterized by CD20 and PAX5 negativity together with the expression of CD38, CD138, MUM1/IRF4, Blimp1, and XBP1 plasmacytic differentiation markers. It is usually associated with Epstein–Barr virus infections, and MYC gene rearrangements. PbL should be carefully differentiated from other CD20-negative B-cell neoplasms, ie, primary effusion lymphoma, anaplastic lymphoma kinase-positive (ALK) large B-cell lymphoma, and LBCL in human herpesvirus 8-associated multicentric Castleman disease. Despite our improved understanding of this disease, its prognosis remains dismal with short overall survival. There is no standard of care for this entity. Several chemotherapy combinations have been used with hardly any differences on its outcome. Thus, new approaches with the addition of novel molecules are needed to overcome its poor prognosis. Our current understanding and knowledge of PbL relies primarily on case reports and small case series. In this review, we revise through an extensive literature search, the clinical and biological characteristics of this entity, and the potential therapeutic options.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85444052","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":"Recent advances in the biology and treatment of B-cell acute lymphoblastic leukemia.","authors":"Mehrdad Hefazi,&nbsp;Mark R Litzow","doi":"10.2147/BLCTT.S170351","DOIUrl":"https://doi.org/10.2147/BLCTT.S170351","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Over the last decade, major advances have been made in our understanding and management of ALL. Identification of new prognostic genomic markers and incorporation of minimal residual diseases' assessment into therapeutic protocols have improved risk stratification and treatment strategies. The use of pediatric-inspired regimens for adolescent and young adults, and the advent of tyrosine kinase inhibitors and novel targeted therapies, including monoclonal antibodies and chimeric antigen receptor T cells, have redefined the therapeutic paradigm of ALL, and significantly improved the outcomes. In this article, we will provide an overview of the current knowledge regarding the biology and treatment of ALL, and highlight recent diagnostic and therapeutic advances made in this area over the past 5 years.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BLCTT.S170351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41215413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current understanding of the role and regulation of miRNAs in Burkitt lymphoma","authors":"A. Videtta, V. Malagnino, G. De Falco","doi":"10.2147/BLCTT.S129618","DOIUrl":"https://doi.org/10.2147/BLCTT.S129618","url":null,"abstract":"Since its discovery in 1958, Burkitt lymphoma (BL) has been extensively studied and has become a model for tumorigenesis, but its pathogenesis has not been completely explained and understood yet. The aim of this review was to summarize the current knowledge about BL and, in particular, to discuss the role of miRNAs in its pathogenesis and their possible use as diagnostic and prognostic indicators. The impact of viral-encoded miRNAs is also discussed, with the Epstein–Barr infection being almost invariably detected in the endemic variant of this tumor.","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88949723","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}