Cristina F Contreras, Christine S Higham, Astrid Behnert, Kailyn Kim, Elliot Stieglitz, Sarah K Tasian
BACKGROUND: The treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (rrALL) has been revolutionized given recent clinical trials demonstrating remarkable success of immunotherapies and leading to drug approvals by United States and European agencies. We report experience with commercial blinatumomab and inotuzumab use at two North American pediatric oncology centers in children and adolescents/young adults with B-ALL. PROCEDURE: Patients 0-25 years old treated with the CD19 × CD3 bispecific T cell-engaging antibody blinatumomab and/or the CD22 antibody-drug conjugate inotuzumab from January 1, 2010, to June 1, 2018, were eligible...
October 24, 2020: Pediatric Blood & Cancer
Yuichiro Uchida, Makoto Yoshimitsu, Miho Hachiman, Shuichi Kusano, Naosuke Arima, Kodai Shima, Maiko Hayashida, Yuhei Kamada, Daisuke Nakamura, Akihiko Arai, Yuetsu Tanaka, Hiromitsu Hara, Kenji Ishitsuka
OBJECTIVES: Adult T-cell leukemia/lymphoma (ATL) is an intractable T-cell malignancy caused by long-term infection with human T-cell leukemia virus type-1 (HTLV-1). While ATL pathogenesis has been associated with HTLV-1-derived oncogenic proteins, including Tax and HBZ, the contribution of genomic aberrations remains poorly defined. METHODS: To elucidate the genomic basis of ATL, whole exome sequencing was performed on cells from 47 patients with aggressive ATL...
October 24, 2020: European Journal of Haematology
Elrazi Ali, Mohamed Badawi, Elabbass Abdelmahmuod, Samah Kohla, Mohamed A Yassin
BACKGROUND COVID-19 is a newly emerging disease that is not yet fully understood. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that is easily transmitted from human to human through the respiratory route. Usually, it presents with fever, headache, fatigue accompanied by respiratory symptoms like cough and dyspnea, and other systemic involvements. Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative neoplasm characterized by absolute lymphocytosis and demonstration of clonality unlike other causes of lymphocytosis...
October 24, 2020: American Journal of Case Reports
Miguel Mendivil-Perez, Carlos Velez-Pardo, Gloria E David-Yepes, Javier E Fox, Marlene Jimenez-Del-Rio
Despite some advances in the treatment of acute lymphoblastic (ALL) and myeloid leukemia (AML) in recent years, there is still a prominent percentage of pediatric patients with a reduced overall prognosis. Therefore, other therapeutic approaches are needed to treat those patients. In the present study, we report that the metal chelator TPEN affected ΔΨm and DNA content in isolated CD34+ refractory cells from bone marrow ALL (n = 7; B-cell, n = 4; T-cell, n = 3) and AML (n = 3) pediatric patients...
October 24, 2020: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Maryam Adib, Seyed Morteza Seifati, Mahmood Dehghani Ashkezari, Fatemeh Akyash, Arezoo Khoradmehr, Behrouz Aflatoonian
Background: Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell development In Vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growth differentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitory factor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM (hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes...
October 2020: International Journal of Fertility & Sterility
Kristi K Fitzgerald, Nina Powell-Hamilton, Amanda J Shillingford, Bradley Robinson, Karen W Gripp
PBX1 encodes the pre-B cell leukemia homeobox transcription factor, a three amino acid loop extension (TALE) homeodomain transcription factor, which forms nuclear complexes with other TALE class homeodomain proteins that ultimately regulate target genes controlling organ patterning during embryogenesis. Heterozygous de novo pathogenic variants in PBX1 resulting in haploinsufficiency are associated with congenital anomalies of the kidneys and urinary tract, most commonly renal hypoplasia, as well as anomalies involving the external ear, branchial arch, heart, and genitalia, and they cause intellectual disability and developmental delay...
October 24, 2020: American Journal of Medical Genetics. Part A
Francisco M Izquierdo, Dimas Suárez-Vilela, Ana de la Hera-Magallanes, Emiliano Honrado
No abstract text is available yet for this article.
October 23, 2020: Journal of Cutaneous Pathology
S Pützer, L Varghese, J von Jan, T Braun, A K Giri, P Mayer, N Riet, S Timonen, S Oberbeck, H Kuusanmäki, S Mustjoki, M-H Stern, T Aittokallio, S Newrzela, A Schrader, M Herling
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
October 23, 2020: Leukemia
Upasana Sunil Arvindam, Paulien M M van Hauten, Dawn Schirm, Nicolaas Schaap, Willemijn Hobo, Bruce R Blazar, Daniel A Vallera, Harry Dolstra, Martin Felices, Jeffrey S Miller
The low 5-year survival rate for patients with acute myeloid leukemia (AML), primarily caused due to disease relapse, emphasizes the need for better therapeutic strategies. Disease relapse is facilitated by leukemic stem cells (LSCs) that are resistant to standard chemotherapy and promote tumor growth. To target AML blasts and LSCs using natural killer (NK) cells, we have developed a trispecific killer engager (TriKETM ) molecule containing a humanized anti-CD16 heavy chain camelid single-domain antibody (sdAb) that activates NK cells, an IL-15 molecule that drives NK-cell priming, expansion and survival, and a single-chain variable fragment (scFv) against human CLEC12A (CLEC12A TriKE)...
October 23, 2020: Leukemia
Md Kamrul Hasan, Emanuela M Ghia, Laura Z Rassenti, George F Widhopf, Thomas J Kipps
Patients with chronic lymphocytic leukemia (CLL) have high plasma-levels of Wnt5a, which can induce phosphorylation of ERK1/2 and enhance CLL-cell proliferation. Such effects could be inhibited by treatment with an ERK1/2 inhibitor, ERK1/2-specific siRNA, or cirmtuzumab, an anti-ROR1 mAb. The CLL-derived line, MEC1, expresses Wnt5a, but not ROR1. MEC1 cells transfected to express ROR1 (MEC1-ROR1) had higher levels of phosphorylated ERK1/2 than parental MEC1, or MEC1 transfected with ROR1ΔPRD, a truncated ROR1 lacking the cytoplasmic proline-rich domain (PRD), or ROR1P808A a mutant ROR1 with a P→A substitution at 808, which is required for complexing with the Rac-specific-guanine-nucleotide-exchange factor DOCK2 upon stimulation with Wnt5a...
October 23, 2020: Leukemia
Marina Kalli, Andrew Blok, Long Jiang, Nichola Starr, Marcos J C Alcocer, Franco H Falcone
Protein microarrays have been successfully used for detection of allergen-specific IgE in patient sera. Here, we demonstrate proof-of-concept of a solid-phase technique coupling the high-throughput potential of protein microarrays with the biologically relevant readout provided by IgE reporter cells, creating a novel allergic sensitization detection system. Three proteins (κ-casein, timothy grass pollen extract, polyclonal anti-human IgE) were printed onto three different polymer-coated surfaces (aldehyde-, epoxy- and NHS ester-coated)...
October 23, 2020: Scientific Reports
(no author information available yet)
In a phase I trial, iadademstat induced blast differentiation and reduced bone marrow blast burden.
October 23, 2020: Cancer Discovery
Erika Borlenghi, Chiara Pagani, Patrizia Zappasodi, Massimo Bernardi, Claudia Basilico, Roberto Cairoli, Nicola Fracchiolla, Elisabetta Todisco, Mauro Turrini, Chiara Cattaneo, Matteo Da Vià, Fabio Ciceri, Francesco Passamonti, Valentina Mancini, Mariarita Sciumè, Elisa Cerqui, Margherita Sciumè, Giuseppe Rossi
OBJECTIVES: Treatment of older patients with acute myeloid leukemia (AML) is still controversial. To facilitate treatment decisions, the "fitness criteria" proposed by Ferrara et al. (Leukemia, 2013), including age > 75 years, performance status and comorbidities, were verified retrospectively in 699 patients with AML (419 de-novo, 280 secondary AML), diagnosed at 8 Hematological Centers (REL). METHODS: Patients were categorized in FIT to intensive chemotherapy (i-T) (292, 42...
October 20, 2020: Journal of Geriatric Oncology
R Rachwani Anil, C Rocha-de-Lossada, F Zamorano Martín, A Santos Ortega, G Luque Aranda, M España Contreras, J Escudero Gómez
No abstract text is available yet for this article.
October 20, 2020: Journal Français D'ophtalmologie
Alberto L Horenstein, Angelo C Faini, Fabio Morandi, Cristiano Bracci, Francesco Lanza, Nicola Giuliani, Aneel Paulus, Fabio Malavasi
Monoclonal antibodies (mAbs) were initially considered as a possible "magic bullet" for in vivo elimination of tumor cells. mAbs represented the first step: however, as they were murine in nature (the earliest experience on the field), they were considered unfit for human applications. This prompted the development of techniques for cloning the variable regions of conventional murine antibodies, genetically mounted on human IgG. The last step in this years-long process was the design for the preparation of fully human reagents...
October 21, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mingmin Tang, Xin Xie, Muran Shi, Wenxiu Xin, Guowan Zheng, Yanhua Zhang, Zhizhen Zhang, Xiaoyuan Lian
BACKGROUND: Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) is a natural polyphenolic ester isolated as a minor component from a water extract of the Chinese medicine Zhongjiefeng [Sarcandra glabra (Thunb.) Nakai (Chloranthaceae)] and has previously shown to have activity against solid tumors through the modulation of multiple targets or signal pathways. However, the activity and potential mechanism of CADPE against leukemia cells have not yet been characterized. PURPOSE: To investigate whether and how CADPE kills leukemia cells...
October 13, 2020: Phytomedicine
Eleonora De Bellis, Tiziana Ottone, Lisa Mercante, Giulia Falconi, Elisa Cugini, Maria Irno Consalvo, Serena Travaglini, Giovangiacinto Paterno, Alfonso Piciocchi, Elisa Linnea Lindfors Rossi, Carmelo Gurnari, Luca Maurillo, Francesco Buccisano, William Arcese, Maria Teresa Voso
The terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in acute myeloid leukemias (AMLs), where it may be involved in the generation of NPM1 and FLT3-ITD mutations. We studied the correlations between TdT expression and FLT3-ITD or NPM1 mutations in primary AML samples, and the impact on patients' survival. TdT expression was analyzed in 143 adult AML patients by flow cytometry as percentage of positivity and mean fluorescence intensity (MFI) on blasts. TdT was positive in 49 samples (34...
October 15, 2020: Leukemia Research
Qian Qian Wang, Hao Ying Hua, Hua Naranmandura, Hong-Hu Zhu
Arsenic trioxide (ATO) has a long history and it is recognized as both poison and drug for more than two thousand years. Since the establishment of ATO as a frontline therapeutic agent for acute promyelocytic leukemia (APL), the survival of APL patients have been greatly improved and APL is tunred from highly fatal to highly curable disease. Mechanistically, ATO can induce PML/RARα fusion protein degradation, causing APL cell differentiation and apoptosis. On the other hand, the side effects such as differentiation syndrome, cardiac conduction abnormalities and liver toxicity are often observed during the ATO treatment of APL in clinic...
October 19, 2020: Toxicology and Applied Pharmacology
Ross A Dickins
No abstract text is available yet for this article.
October 22, 2020: Blood
Kentaro Yonekura, Shigeru Kusumoto, Ilseung Choi, Nobuaki Nakano, Asahi Ito, Youko Suehiro, Yoshitaka Imaizumi, Makoto Yoshimitsu, Kisato Nosaka, Eiichi Ohtsuka, Michihiro Hidaka, Tatsuro Jo, Hidenori Sasaki, Yukiyoshi Moriuchi, Masao Ogata, Hiro Tatetsu, Kenji Ishitsuka, Yasushi Miyazaki, Ryuzo Ueda, Atae Utsunomiya, Takashi Ishida
Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65-specific cytotoxic T lymphocytes (CMV-CTLs)...
October 27, 2020: Blood Advances
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