Supawadee Umthong, Brian Lynch, Uddhav Timilsina, Brandon Waxman, Emily B Ivey, Spyridon Stavrou
The membrane-associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2, and 8 are antiretroviral factors that target the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination...
March 2, 2021: MBio
Barina Aqil, Wei Xie, M Tarek Elghetany, Reka Szigeti
OBJECTIVE: The value of bronchoalveolar lavage (BAL) in the diagnosis of pulmonary diseases of diverse etiologies is widely accepted. Cytospin and cell-block preparations for cytomorphological (CM) evaluation and for immunohistochemical studies are the standard method to evaluate BAL, though it may be time-consuming. Flow cytometric (FC) evaluation, on the other hand, has a short turnaround time, and is a useful methodology to differentiate reactive processes from hematological neoplasms, or detect a small aberrant population in an inflammatory background...
January 2021: Annals of Clinical and Laboratory Science
Naomi Hirako, Shinichiro Takahashi
Downregulation of the myeloid master regulator Spi1 /PU.1 plays a pivotal role in leukemogenesis, and we previously showed that Spi1 /PU.1 directly represses metallothionein (MT)-1G through the epigenetic activity of PU.1. Furthermore, we recently demonstrated that overexpression of MT-1G inhibits retinoic acid-induced differentiation of acute promyelocytic leukemia NB4 cells. As PU.1 is a master regulator of growth and differentiation in myeloid cells, we examined its effects on cell proliferation of MT-1G -overexpressing NB4 (NB4MTOE) cells in the present study...
January 2021: Annals of Clinical and Laboratory Science
Aixia Hu, Fan Hong, Daohong Li, Yuwei Jin, Lingfei Kon, Ziguang Xu, Hui He, Qi Xie
BACKGROUND: As a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer. METHODS: RT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells...
March 2, 2021: Journal of Translational Medicine
Ferdane Danışman-Kalındemirtaş, Serap Erdem-Kuruca, Kadriye Akgün-Dar, Zeynep Karakaş, Özge Soylu, Nilgün Karali
AIM: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3-thiosemicarbazone derivatives. These compounds could be promissing anticancer agents in leukemia treatment. BACKGROUND: Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to non-specificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life...
March 1, 2021: Anti-cancer Agents in Medicinal Chemistry
Sanjal Desai, Clifton Mo, Erika M Gaglione, Constance M Yuan, Maryalice Stetler-Stevenson, Xin Tian, Irina Maric, Laura Wake, Mohammed Z Farooqui, Dennis C Drinkwater, Susan Soto, Janet Valdez, Thomas E Hughes, Pia Nierman, Jennifer Lotter, Gerald E Marti, Christopher Pleyer, Clare Sun, Jeanine Superata, Cydney Nichols, Sarah E M Herman, Margaret A Lindorfer, Ronald P Taylor, Adrian Wiestner, Inhye E Ahn
High-risk cytogenetics and minimal residual disease (MRD) after chemoimmunotherapy (CIT) predict unfavorable outcome in chronic lymphocytic leukemia (CLL). This phase 2 study investigated risk-adapted CIT in treatment-naïve CLL (NCT01145209). Patients with high-risk cytogenetics received induction with fludarabine, cyclophosphamide, and ofatumumab. Those without high-risk cytogenetics received fludarabine and ofatumumab. After induction, MRD positive (MRD+) patients received 4 doses of ofatumumab consolidation...
March 2, 2021: Leukemia & Lymphoma
Sujin Choi, Jung Yoon Choi, Bo Kyung Kim, Hong Yul Ahn, Kyung Taek Hong, Jung-Eun Cheon, Hee Young Shin, Hyoung Jin Kang
Imatinib is a BCR-ABL tyrosine kinase inhibitor used for the treatment of a variety of diseases including Philadelphia chromosome positive (Ph+) leukemia. We report a 15 year old male patient presenting with symptomatic acute intracerebral hemorrhage (ICH) in midbrain while on imatinib more than three years after completion of therapy for Ph + B-ALL. The patient denied recent trauma history and consumption of other medication. Laboratory findings did not show any signs of relapse, coagulopathy nor thrombocytopenia...
March 3, 2021: Pediatric Hematology and Oncology
Gesualda M Gulino, Francesca Bruno, Valentina Sturiale, Desiree Brancato, Denise Ragusa, Sabrina Tosi, Salvatore Saccone, Concetta Federico
Fluorescence in situ hybridization (FISH) and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus and are applied here to study the organization of genes ( LMBR1 , NOM1 , MNX1 , UBE3C , PTPRN2 ) localized in the human 7q36.3 band. This region contains the MNX1 gene, which is normally not expressed in human lymphocytes beyond embryonic development. However, this homeobox gene is frequently activated in leukemic cells and its expression is associated with an altered gene positioning in the leukemia cell nuclei...
February 26, 2021: International Journal of Molecular Sciences
Nienke Visser, Harm Jan Lourens, Gerwin Huls, Edwin Bremer, Valerie R Wiersma
Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines...
February 26, 2021: International Journal of Molecular Sciences
Evangelos Koustas, Panagiotis Sarantis, Michalis V Karamouzis, Philippe Vielh, Stamatios Theocharis
Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 ( EWSR1 ) and FLI1 (Friend leukemia virus integration site 1) genes, leading to an EWS-FLI1 fused protein, which is associated with autophagy, a homeostatic and catabolic mechanism under normal and pathological conditions. Following such interesting and controversial data regarding autophagy in ES, many clinical trials using modulators of autophagy are now underway in this field...
February 26, 2021: Biomolecules
Kanwal Mahmood, Ashkan Emadi
Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Studies in hematological malignancies have shown alterations in fatty acid, folate, and amino acid metabolism pathways in cancer cells. One-carbon (1-C) metabolism is essential for numerous cancer cell functions, including protein and nucleic acid synthesis and maintaining cellular redox balance, and inhibition of the 1-C pathway has yielded several highly active drugs, such as methotrexate and 5-FU...
February 26, 2021: Pharmaceuticals
Gulam Mohmad Rather, Michael Anyanwu, Tamara Minko, Olga Garbuzenko, Zoltan Szekely, Joseph R Bertino
BACKGROUND: We tested the antitumor effects of a modified E2F peptide substituting D-Arg for L-Arg, conjugated to penetratin (PEP) against solid tumor cell lines and the CCRF-leukemia cell line, alone and in combination with pemetrexed or with cisplatin. For in - vivo studies, the peptide was encapsulated in PEGylated liposomes (PL-PEP) to increase half-life and stability. METHODS: Prostate cancer (DU145 and PC3), breast cancer (MCF7, MDA-MB-468, and 4T1), lymphoma (CCRF-CEM), and non-small cell lung cancer (NSCLC) cell lines (H2009, H441, H1975, and H2228) were treated with D-Arg PEP in combination with cisplatin or pemetrexed...
February 26, 2021: Cancers
Camila V Ramos, Vera C Martins
Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. In the thymus, cell competition was addressed in thymus transplantation experiments, and found to be a homeostatic process that contributes to thymus turnover...
February 27, 2021: Developmental Biology
Pablo Elías Morande, Xiao-Jie Yan, Julieta Haydee Sepulveda-Yanez, Noé Seija, Maria Elena Marquez, Natalia Soledad Sotelo, Cecilia Abreu, Martina Crispo, Gabriel Fernández-Graña, Natalia Rego, Therence Bois, Stephen Patrick Methot, Florencia Palacios, Victoria Remedi, Kanti R Rai, Alejandro Buschiazzo, Javier Marcelo Di Noia, Marcelo Alejandro Navarrete, Nicholas Chiorazzi, Pablo Oppezzo
Most cancers become more dangerous by the outgrowth of malignant subclones with additional DNA mutations that favor proliferation or survival. Using chronic lymphocytic leukemia (CLL), a disease exemplary of this process, and a model for neoplasms in general, we created transgenic mice overexpressing the enzyme, activation-induced deaminase (AID), whose normal function is to induce DNA mutations in B lymphocytes. AID allows normal B lymphocytes to develop more effective immunoglobulin (Ig)-mediated immunity, but also is able to mutate non-Ig genes, predisposing to cancer...
March 2, 2021: Blood
Hugues de The, Cécile Esnault, Marie-Claude Geoffroy
The retinoic acid receptors (RARA, RARB, RARG) are ligand-regulated nuclear receptors which act as transcriptional switches. These master genes drew significant interest in the 1990s due to their key roles in embryogenesis and involvement in a rare malignancy, acute promyelocytic leukemia (APL), in which the RARA (and very rarely RARG or RARB) genes are rearranged, underscoring the central role of deregulated retinoid signaling in leukemogenesis. A number of recent provocative observations have revived interest in the roles of retinoids in non-APL acute myeloid leukemia (AMLs), as well as in normal hematopoietic differentiation...
March 2, 2021: Blood
Candida Vitale, Chiara Salvetti, Valentina Griggio, Marika Porrazzo, Luana Schiattone, Giulia Zamprogna, Andrea Visentin, Francesco Vassallo, Ramona Cassin, Gian Matteo Rigolin, Roberta Murru, Luca Laurenti, Paolo Rivela, Monia Marchetti, Elsa Pennese, Massimo Gentile, Elia Boccellato, Francesca Perutelli, Maria Chiara Montalbano, Lorenzo De Paoli, Gianluigi Reda, Lorella Orsucci, Livio Trentin, Antonio Cuneo, Alessandra Tedeschi, Lydia Scarfò, Gianluca Gaidano, Francesca Romana Mauro, Robin Foà, Mario Boccadoro, Marta Coscia
Autoimmune cytopenias (AIC) affect 5-9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs - ibrutinib, idelalisib and venetoclax - have a prominent role in the treatment of CLL, but their impact on CLL-associated AIC is largely unknown. In this study, we evaluated the characteristics and outcome of pre-existing AIC, and described the incidence, quality and management of treatment-emergent AIC during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody)...
March 2, 2021: Blood
D A R Castelijn, M J Wondergem, D M Heijink
A 65-year-old female complained of diffuse and rapidly progressive gingival enlargement. Gingival overgrowth can be caused by medication, infections or systemic diseases. In case of generalized, quickly progressive gingival enlargement, acute myeloid leukemia should be considered. Blood results showed an acute myelomonocytic leukemia. Treating the leukemia resolved the symptoms.
February 3, 2021: Nederlands Tijdschrift Voor Geneeskunde
Foulon S, Cony-Makhoul P, Guerci-Bresler A, Daban M, Kapso R, Tubert-Bitter P, Bonastre J
PURPOSE: Tyrosine kinase inhibitors (TKIs) have dramatically improved the prognosis of chronic myeloid leukemia (CML). We aimed to assess health state utility and quality of life (QoL) in French patients with CML in real-life setting, to study the determinants of utility score and to compare health-related QoL values to general population norms. METHODS: We conducted a cross-sectional study in 412 patients with CML. Data were collected by electronic survey. Three patient-reported outcomes questionnaires were used: EORTC QLQ-C30, EORTC QLQ-CML24 and EuroQol EQ-5D-3L...
March 2, 2021: Quality of Life Research
Hiroshi Ureshino
Chronic myeloid leukemia (CML) is caused by the reciprocal translocation t(9;22)(q34;q11), resulting in the BCR-ABL1 fusion gene. BCR-ABL1 tyrosine kinase inhibitors (TKIs) improve overall survival in patients with chronic phase CML (CML-CP). Approximately half of the patients who achieve a durable deep molecular response can achieve sustained treatment-free remission (TFR) after TKI discontinuation; thus TFR is now a therapeutic goal for most patients with CML-CP. Sensitive BCL-ABL1 transcript detection methods reveal that evidence of residual CML cells remains in patients who achieve sustained TFR, indicating that the host immune system protects against CML relapse...
March 2, 2021: International Journal of Hematology
Xiaoming Liu, Yao Zou, Li Zhang, Xiaojuan Chen, Wenyu Yang, Ye Guo, Yumei Chen, Yingchi Zhang, Xiaofan Zhu
PURPOSE: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is rare in China and case reports are varied. We conducted an in-depth analysis of newly diagnosed children with T-ALL from January 1999 to April 2015 in our center, to show the biological differences between Chinese ETP-ALL children and other immune types of T-ALL. METHODS: The newly diagnosed children with T-ALL were divided into four groups according to their immunophenotype: ETP-ALL, early non-ETP-ALL, cortical T-ALL and medullary T-ALL...
March 2, 2021: Journal of Cancer Research and Clinical Oncology
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