Vincent M De La Porte, Martin Lammens, Sven Dekeyzer, Michel Van Lint
PURPOSE: To report combined central arterial and venous occlusions secondary to bilateral leukemic interfascicular optic nerve infiltration in a 56-year-old man. This was the sole presentation of a relapse in T/Myeloid mixed-phenotype acute leukemia after 5 months of remission. METHODS: Case report with clinical photography. RESULTS: A 56-year-old man reported to be in complete remission of T/Myeloid mixed-phenotype acute leukemia (MPAL) presented with sudden painless loss of vision in his left eye...
September 19, 2021: Retinal Cases & Brief Reports
Masatoshi Haruta, Kensaku Iwata, Shigeo Yoshida
PURPOSE: To report a case of bilateral proliferative diabetic retinopathy and lipemia retinalis in a patient with acquired lipodystrophy. METHODS: A retrospective case report. RESULTS: A 23-year-old woman with a diagnosis of acquired lipodystrophy was referred for ophthalmic evaluation. She had been diagnosed with acute lymphocytic leukemia at the age of 3 years and undergone hematopoietic stem cell transplantation. Best-corrected visual acuity was 20/20 in both eyes; however, funduscopy revealed bilateral diabetic retinopathy and lipemia retinalis, neither of which was apparent 2 years earlier...
July 16, 2021: Retinal Cases & Brief Reports
Rachel A Harris, Jadd M Stevens, Diane L Pickering, Pamela A Althof, Lynette M Smith, Jennifer N Sanmann, Bhavana J Dave
The clinical implications of deletions within chromosome 14q32 in CLL pathogenesis remain unclear. We examined the frequency of 14q32 deletions among CLL cases by karyotype and FISH, categorized the variation using genomic microarray, and assessed the prognostic impact by time-to-first-treatment (TTFT) analysis. A 14q32 abnormality was detected in 35 % (245/698) of cases, with the majority containing a 5' partial telomeric 14q32 deletion. These deletions within the IGH variable region (35/40) ranged from 236 kb to 1...
July 11, 2021: Leukemia Research
Siba El Hussein, Joseph D Khoury, L Jeffrey Medeiros
B-prolymphocytic leukemia (B-PLL) is included as a distinct entity in the current World Health Organization classification of hematolymphoid neoplasms. However, the diagnosis of B-PLL has presented several challenges since its conception, and over the past decades investigations of B-PLL have revealed substantial biologic and molecular heterogeneity. These data have shown that many B-PLL cases present many similarities with other types of small B-cell lymphomas, and that small B-cell lymphomas can undergo prolymphocytoid transformation...
July 16, 2021: Annals of Diagnostic Pathology
Wenli Zhou, Zhennan Yun, Ting Wang, Chao Li, Jiantao Zhang
The critical roles of transcription factors in cell differentiation and the delineation of cell phenotypes have been reported. The current study aimed to characterize the functions of the basic transcription factor 3 (BTF3) gene and its regulation of the intestinal stem cell marker B cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) gene in colorectal cancer (CRC). Stem cell-like traits and epithelial-mesenchymal transition (EMT) of cultured human CRC cell line HCT116 were evaluated by CD133+ subpopulation counting, colony formation, tumorosphere generation, and expression of EMT-specific markers and stem cell markers...
July 19, 2021: International Journal of Biological Macromolecules
Yiming Wang, Wei Xu, Hao Wu, Wenli Zhang, Cuie Guang, Wanmeng Mu
L-Asparaginase (L-ASNase, EC, an antitumor drug for acute lymphoblastic leukemia (ALL) therapy, is widely used in the clinical field. Similarly, L-ASNase is also a powerful and significant biological tool in the food industry to inhibit acrylamide (AA) formation. This review comprehensively summarizes the latest achievements and improvements in the production, modification, and application of microbial L-ASNase. To date, the expression levels and optimization of expression hosts such as Escherichia coli, Bacillus subtilis, and Pichia pastoris, have made significant progress...
July 19, 2021: International Journal of Biological Macromolecules
Amit Subedi, Qiang Liu, Dhanoop M Ayyathan, David Sharon, Severine Cathelin, Mohsen Hosseini, Changjiang Xu, Veronique Voisin, Gary D Bader, Angelo D'Alessandro, Eric R Lechman, John E Dick, Mark D Minden, Jean C Y Wang, Steven M Chan
Current treatments for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), which perpetuate the disease. Here, we performed a metabolic drug screen to identify LSC-specific vulnerabilities and found that nicotinamide phosphoribosyltransferase (NAMPT) inhibitors selectively killed LSCs, while sparing normal hematopoietic stem and progenitor cells. Treatment with KPT-9274, a NAMPT inhibitor, suppressed the conversion of saturated fatty acids to monounsaturated fatty acids, a reaction catalyzed by the stearoyl-CoA desaturase (SCD) enzyme, resulting in apoptosis of AML cells...
July 12, 2021: Cell Stem Cell
C Ojeda Sánchez, J Segú-Tell, D Gomez-Barroso, E Pardo Romaguera, J A Ortega-García, R Ramis
BACKGROUND: Childhood leukemia is the most common childhood cancer. To date, few risk factors related to predisposition have been identified; therefore, new hypotheses should be considered. OBJECTIVE: To explore the possible relationship of residential proximity to urban green spaces on childhood leukemia. METHODS: We conducted a population-based case control study in the metropolitan area of Madrid from 2000 to 2015. It included 383 incident cases and 1935 controls, individually matched by birth year, sex and area of residence...
July 19, 2021: Environmental Research
Si-Liang Chen, Hui Zhang, Robert Peter Gale, Jing-Yan Tang, Ching-Hon Pui, Sai-Juan Chen, Yang Liang
This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement...
July 2021: JCO global oncology
Fisihatsion Tadesse, Getahun Asres, Abdulaziz Abubeker, Amha Gebremedhin, Jerald Radich
PURPOSE: Despite the successes achieved in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy, resistance remains an obstacle. The most common mechanism of resistance is the acquisition of a point mutation in the BCR-ABL kinase domain. Few studies have reported African patients with CML in regard to such mutations. We here report the types of BCR-ABL mutations in Ethiopian imatinib-resistant patients with CML and their outcome. PATIENTS AND METHODS: Patients with CML with a diagnosis of imatinib resistance who were tested for BCR-ABL mutation between 2014 and September 2019 were included...
July 2021: JCO global oncology
Athanasios Tragiannidis, Andreas H Groll
Targeted therapies have emerged as innovative treatments for patients whose disease does not respond to conventional chemotherapy, and their use has widely expanded in the field of pediatric hematologic malignancies in the last decade. While they carry the promise of improved disease control and survival and are currently investigated in first-line treatment protocols for patients with poor prognostic markers, they are associated with a considerable incidence of specific toxicities, including cytokine-release syndrome, neurotoxicity, hepatotoxicity, nephrotoxicity, cardiotoxicity, endocrine adverse events, and infectious complications...
July 22, 2021: Paediatric Drugs
Zhe Wang, Xiaoyu Wang, Zhen Wang, Yuyi Feng, Yaqin Jia, Lili Jiang, Yangliu Xia, Jun Cao, Yong Liu
Importance: Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity. Objective: To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit. Data Sources: PubMed, Embase, Cochrane library databases, and ClinicalTrials...
July 1, 2021: JAMA Network Open
Mahasweta Gooptu, Rizwan Romee, Andrew St Martin, Mukta Arora, Monzr Al Malki, Joseph H Antin, Christopher N Bredeson, Claudio G Brunstein, Saurabh Chhabra, Ephraim J Fuchs, Nilanjan Ghosh, Michael R Grunwald, Christopher G Kanakry, Natasha Kekre, Jospeh P McGuirk, Ian K McNiece, Rohtesh S Mehta, Marco Mielcarek, Fillipo Milano, Dipenkumar Modi, Ran Reshef, Scott R Solomon, Mark A Schroeder, Edmund K Waller, Yoshiro Inamoto, Robert J Soiffer, Mary Eapen
Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018...
July 22, 2021: Blood
Jong Bok Lee, Dilshad H Khan, Rose Hurren, Mingjing Xu, Yoosu Na, Hyeonjeong Kang, Sara Mirali, Xiaoming Wang, Marcela Gronda, Yulia Jitkova, Neil MacLean, Andrea Arruda, Zoe Alaniz, Marina Y Konopleva, Michael Andreeff, Mark D Minden, Li Zhang, Aaron D Schimmer
Venetoclax, a Bcl-2 inhibitor, in combination with the hypomethylating agent azacytidine, achieves complete remission with or without count recovery in ∼70% of treatment-naive elderly patients unfit for conventional intensive chemotherapy. However, the mechanism of action of this drug combination is not fully understood. We discovered that venetoclax directly activated T cells to increase their cytotoxicity against acute myeloid leukemia (AML) in vitro and in vivo. Venetoclax enhanced T-cell effector function by increasing reactive oxygen species generation through inhibition of respiratory chain supercomplexes formation...
July 22, 2021: Blood
Pablo Elías Morande, Xiao-Jie Yan, Julieta Sepulveda, Noé Seija, María Elena Marquez, Natalia Sotelo, Cecilia Abreu, Martina Crispo, Gabriel Fernández-Graña, Natalia Rego, Therence Bois, Stephen P Methot, Florencia Palacios, Victoria Remedi, Kanti R Rai, Alejandro Buschiazzo, Javier M Di Noia, Marcelo A 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 that exemplifies this process and is a model for neoplasms in general, we created transgenic mice overexpressing the enzyme activation-induced deaminase (AID), which has a normal function of inducing DNA mutations in B lymphocytes. AID not only allows normal B lymphocytes to develop more effective immunoglobulin-mediated immunity, but is also able to mutate nonimmunoglobulin genes, predisposing to cancer...
July 22, 2021: Blood
Amelie Sandart, Arja Harila-Saari, Henrik Arnell, Björn Fischler, Jukka Vakkila
OBJECTIVES: The prevalence and significance of liver involvement at diagnosis was studied in pediatric acute lymphoblastic (ALL) and myeloid leukemia (AML). METHODS: A population based cohort of 122 pre B-ALL, 22 T-ALL and 45 AML patients was formed from the Nordic Society of Pediatric Hematology and Oncology leukemia registries (years 2005 - 2017). Hepatomegaly, elevated ALT, high INR, hypoalbuminemia and conjugated hyperbilirubinemia at diagnosis were used as markers for liver involvement...
July 20, 2021: Journal of Pediatric Gastroenterology and Nutrition
Tomás Palanques-Pastor, Juan Eduardo Megías-Vericat, Pilar Martínez, José Luis López Lorenzo, Javier Cornago Navascués, Gabriela Rodriguez Macias, Isabel Cano, Montserrat Arnan Sangerman, María Belén Vidriales Vicente, Jesús Lorenzo Algarra Algarra, María Ángeles Foncillas, Pilar Herrera, Carmen Botella Prieto, Susana Vives, Ángela Figuera Álvarez, Laida Cuevas Palomares, Marta Sobas, Alejandro Contento Gonzalo, Rebeca Cuello García, María Elena Amutio Diez, Dunia De Miguel Llorente, Begoña Navas Elorza, Juan Miguel Bergua Burgues, Teresa Bernal Del Castillo, María Carmen Mateos Rodríguez, Erik de Cabo López, Ana Carolina Franco Villegas, Raimundo García Boyero, Cristian Escolano Escobar, Cristina Seri Merino, Carlos Cervero, Alicia Roldán Pérez, Lourdes Hermosín Ramos, Marta Cervera Calvo, María Telesa Olave, Paola Villafuerte Gutiérrez, Almudena de Laiglesiai, Josefina Serrano, María Josefa Najera Irazu, José Luis Piñana, Miguel Ángel Sanz, Joaquín Martínez-López, Pau Montesinos
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces higher morbidity and mortality in hematological malignancies, but evidence in acute myeloid leukemia (AML) is scarce. A multicenter observational study was conducted to determine the clinical outcomes and assess the impact of therapeutic approaches in adult AML patients with SARS-CoV-2 infection in the first wave (March-May 2020). Overall, 108 patients were included: 51.9% with active leukemia and 70.4% under therapeutic schedules for AML...
July 22, 2021: Leukemia & Lymphoma
Sara Artigas-Jerónimo, Margarita Villar, Agustín Estrada-Peña, Adrián Velázquez-Campoy, Pilar Alberdi, José de la Fuente
The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes (BPs) such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In the present study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells...
July 30, 2021: Bioscience Reports
Darlene A Monlish, Kevin J Beezhold, Pailin Chiaranunt, Katelyn Paz, Nathan J Moore, Andrea K Dobbs, Rebecca A Brown, John A Ozolek, Bruce R Blazar, Craig A Byersdorfer
Allogeneic hematopoietic stem cell transplantation is a viable treatment for multiple hematologic diseases, but its application is often limited by graft-versus-host disease (GVHD), where donor T cells attack host tissues in the skin, liver, and gastrointestinal tract. Here, we examined the role of the cellular energy sensor AMP kinase (AMPK) in alloreactive T cells during GVHD development. Early posttransplant, AMPK activity increased more than 15-fold in allogeneic T cells, and transplantation of T cells deficient in both AMPKα1 and AMPKα2 decreased GVHD severity in multiple disease models...
July 22, 2021: JCI Insight
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