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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#2
Edmond S K Ma
Characteristic chromosomal translocations are found to be associated with subtypes of B-cell non-Hodgkin lymphoma (NHL), for example t(8;14)(q24;q32) and Burkitt lymphoma, t(14;18)(q32;q21) and follicular lymphoma, and t(11;14)(q13;q32) in mantle cell lymphoma. Only few recurrent cytogenetic aberrations have been identified in the T-cell NHL and the best known is the ALK gene translocation t(2;5)(p23;q35) in anaplastic large cell lymphoma. Since lymph node or other tissue is seldom submitted for conventional cytogenetics study, alternative approaches for translocation detection are polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910012/chromosome-preparation-for-chronic-lymphoid-malignancies
#3
Dorota Koczkodaj, Agata A Filip
Conventional cytogenetics is invariably one of the most important methods used in diagnostics of chronic lymphoproliferations. It complements fluorescence in situ hybridization (FISH) and molecular analysis. Presence of particular chromosomal alterations in chronic lymphocytic leukemia enables patients' stratification into appropriate cytogenetic risk groups and influences treatment decisions. In other non-Hodgkin lymphomas cytogenetic analyses are employed also in minimal residual disease assessment.As lymphocytes in chronic lymphoid malignancies are characterized by low proliferation rate in vitro, it is critical to induce their division in the culture properly...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909467/invasive-squamous-cell-carcinoma-of-the-scalp-and-calvarium-a-multidisciplinary-approach
#4
Jennifer Stark, Silvio Podda, Karen Szymanski
Objective: The correlation between immunosuppression-associated skin cancer and lymphoma has been well established. This includes squamous cell carcinoma and chronic lymphocytic leukemia. When a lesion requires excision, reconstruction can be challenging based on the depth and size of the tumor. We present a patient with chronic lymphocytic leukemia and invasive squamous cell carcinoma of the scalp that extended through the calvarium to the dura mater. His tumors were badly neglected for a long period of time and presented at an advanced stage...
2016: Eplasty
https://www.readbyqxmd.com/read/27905140/herpes-simplex-infection-simulating-richter-transformation-a-series-of-four-cases-and-review-of-the-literature
#5
Alireza Salem, Sanam Loghavi, Joseph D Khoury, Rose Lou Marie C Agbay, Jeffrey L Jorgensen, Jeffrey L Medeiros
AIMS: Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and is associated with a poor outcome. Histologic manifestations of RT are variable and include an increase in the proportion of large cells including prolymphocytes, immunoblasts and other pleomorphic cells along with an increased proliferation rate and often necrosis. Rarely, superimposed Herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically...
December 1, 2016: Histopathology
https://www.readbyqxmd.com/read/27904766/the-role-of-pim1-in-the-ibrutinib-resistant-abc-subtype-of-diffuse-large-b-cell-lymphoma
#6
Hsu-Ping Kuo, Scott A Ezell, Sidney Hsieh, Karl J Schweighofer, Leo Wk Cheung, Shiquan Wu, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Yu Liang, Jeff Hsu, Chun-Te Chen, Darrin Beaupre, Betty Y Chang
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma and the most common subtype of non-Hodgkin lymphoma, accounting for roughly 30% of newly diagnosed cases in the United States. DLBCL can be separated into the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, with distinct gene expression profiles, oncogenic aberrations, and clinical outcomes. ABC-DLBCL is characterized by chronically active B-cell receptor (BCR) signaling that can be modulated by Bruton's tyrosine kinase (BTK) activity...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904736/the-biology-behind-b-cell-lymphoma-2-as-a-target-in-chronic-lymphocytic-leukemia
#7
REVIEW
Valentín Ortíz-Maldonado, Pablo Mozas, Julio Delgado
B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904177/a-clinicopathological-analysis-of-primary-cutaneous-lymphomas-a-6-year-observational-study-at-a-tertiary-care-center-of-south-india
#8
Anza Khader, Shiny Padinjarayil Manakkad, Mohammed Shaan, Sarita Sasidharan Pillai, Najeeba Riyaz, P Binitha Manikoth, Muhammed Kunnummel, Sunitha Balakrishnan
BACKGROUND: Little data are available concerning clinical and pathological patterns of cutaneous lymphomas in India. AIM: To analyze the clinical and histopathological characteristics of cutaneous lymphomas in Indian patients. MATERIALS AND METHODS: This is a single-center, prospective, observational study carried out from January 1, 2010, to December 31, 2015. The patients underwent clinical examination, human T-cell lymphotropic virus-1 (HTLV-1) screening, skin biopsy with hematoxylin and eosin and immunohistochemistry staining...
November 2016: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/27903986/adult-t-cell-leukemia-aggressivenness-correlates-with-loss-of-both-5-hydroxymethylcytosine-and-tet2-expression
#9
Ambroise Marçais, Laetitia Waast, Julie Bruneau, Katia Hanssens, Vahid Asnafi, Philippe Gaulard, Felipe Suarez, Patrice Dubreuil, Antoine Gessain, Olivier Hermine, Claudine Pique
Mutations in TET2, encoding one of the TET members responsible for the conversion of DNA cytosine methylation to hydroxymethylation (5-hmc), have been recently described in Human T-lymphotropic virus type 1-associated adult T-cell leukemia/lymphoma (ATLL). However, neither the amount of genomic 5-hmc in ATLL tumor cells nor TET2 expression has been studied yet. In this study, we analyzed these two parameters as well as the mutational status of TET2 in ATLL patients. By employing a direct in situ approach, we documented that tumor T cells infiltrating lymph nodes exhibit low level of 5-hmc compared to residual normal T cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900028/tumor-necrosis-factor-%C3%AE-induced-protein-8-like-1-promotes-apoptosis-by-regulating-b-cell-leukemia-lymphoma-2-family-proteins-in-raw264-7-cells
#10
Yinan Wang, Yao Liu, Chunfang Hu, Xiaoyan Ni, Xiaobo Huang
Although the newly identified protein tumor necrosis factor α-induced protein 8-like 1 (TNFAIP8L1), also known as TIPE1, has been reported to be able to induce apoptosis in human hepatocellular carcinoma cells, the involvement of TIPE1 in apoptosis remains to be elucidated. The present study investigated the pro-apoptotic effect of TIPE1 in an murine macrophage cell line, RAW264.7. The cell apoptosis rate was detected by flow cytometry. The results revealed that overexpressed TIPE1 could directly enhance the apoptosis and the cisplatin-induced cell death of RAW264...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899442/early-generated-b1-b-cells-with-restricted-bcrs-become-chronic-lymphocytic-leukemia-with-continued-c-myc-and-low-bmf-expression
#11
Kyoko Hayakawa, Anthony M Formica, Joni Brill-Dashoff, Susan A Shinton, Daiju Ichikawa, Yan Zhou, Herbert C Morse, Richard R Hardy
In mice, generation of autoreactive CD5(+) B cells occurs as a consequence of BCR signaling induced by (self)-ligand exposure from fetal/neonatal B-1 B cell development. A fraction of these cells self-renew and persist as a minor B1 B cell subset throughout life. Here, we show that transfer of early generated B1 B cells from Eμ-TCL1 transgenic mice resulted in chronic lymphocytic leukemia (CLL) with a biased repertoire, including stereotyped BCRs. Thus, B1 B cells bearing restricted BCRs can become CLL during aging...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27899193/genetic-predisposition-to-leukemia-and-other-hematologic-malignancies
#12
REVIEW
Simone Feurstein, Michael W Drazer, Lucy A Godley
In this review, we provide an overview of familial myelodysplastic syndromes (MDS)/acute leukemia (AL) and bone marrow failure syndromes, as well as insights into familial myeloproliferative neoplasms (MPNs), familial multiple myeloma (MM), familial Waldenström macroglobulinemia (WM), familial lymphoma, and cancer predisposition syndromes with increased risk of MDS/AL. This field will continue to accelerate as next-generation sequencing (NGS) techniques identify novel predisposition alleles in families with a genetic predisposition to hematologic malignancies...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27896941/patient-reported-neuropathic-pain-in-adolescent-and-young-adult-cancer-patients
#13
Melissa A Acquazzino, Eva C Igler, Mahua Dasgupta, Pippa Simpson, Meghen B Browning, Amanda M Brandow
BACKGROUND: Neuropathic pain, a known complication of cancer and its treatments, negatively impacts quality of life. There are limited data using screening tools to aid in the diagnosis of neuropathic pain in cancer patients. Our primary objective was to determine the proportion of adolescent and young adult cancer patients reporting neuropathic pain on a patient-completed, neuropathic pain screening tool. PROCEDURES: This prospective, cohort study enrolled patients 14-39 years of age who were receiving therapy for primary cancer diagnosis, cancer relapse, or had recently completed treatment...
November 28, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27895788/effects-of-microrna-21-on-the-biological-functions-of-t-cell-acute-lymphoblastic-lymphoma-leukemia
#14
Cunzhen Shi, Xudong Zhang, Xin Li, Lei Zhang, Ling Li, Zhenchang Sun, Xiaorui Fu, Jingjing Wu, Yu Chang, Wencai Li, Qingjiang Chen, Mingzhi Zhang
Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is significantly upregulated in tumor tissue. However, its association with T-cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The aim of the present study was to investigate the effects of miR-21 on T-ALL cells by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse transcription-quantitative polymerase chain reaction and western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895780/curcumin-potentiates-the-effect-of-chemotherapy-against-acute-lymphoblastic-leukemia-cells-via-downregulation-of-nf-%C3%AE%C2%BAb
#15
Helia Judith Pimentel-Gutiérrez, Lucina Bobadilla-Morales, César Cenobio Barba-Barba, Citlalli Ortega-De-La-Torre, Fernando Antonio Sánchez-Zubieta, Jorge Román Corona-Rivera, Betsy Annel González-Quezada, Juan S Armendáriz-Borunda, Rocío Silva-Cruz, Alfredo Corona-Rivera
Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895482/nanoparticle-based-strategy-for-personalized-b-cell-lymphoma-therapy
#16
Nicola M Martucci, Nunzia Migliaccio, Immacolata Ruggiero, Francesco Albano, Gaetano Calì, Simona Romano, Monica Terracciano, Ilaria Rea, Paolo Arcari, Annalisa Lamberti
B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27893842/t-cell-receptor-v%C3%AE-staining-identifies-the-malignant-clone-in-adult-t-cell-leukemia-and-reveals-killing-of-leukemia-cells-by-autologous-cd8-t-cells
#17
Aileen G Rowan, Aviva Witkover, Anat Melamed, Yuetsu Tanaka, Lucy B M Cook, Paul Fields, Graham P Taylor, Charles R M Bangham
There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1) to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27891503/tp53-gene-status-affects-survival-in-advanced-mycosis-fungoides
#18
Gitte Wooler, Linea Melchior, Elisabeth Ralfkiaer, Lise Mette Rahbek Gjerdrum, Robert Gniadecki
TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF), the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations, and their prognostic significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-anti-tumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#19
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 mAb such as rituximab have proven highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody dependent cellular cytotoxicity, antibody dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-chronic lymphocytic leukemia (B-CLL). We hypothesized that immune stimulation through TLR7 agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term anti-tumor immune responses...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#20
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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