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Acute T Lymphoblastic Leukemia

Insha Ullah, Sudhir Paul, Zhenjie Hong, You-Gan Wang
MOTIVATION: Under two biologically different conditions, we are often interested in identifying differentially expressed genes. It is usually the case that the assumption of equal variances on the two groups is violated for many genes where a large number of them are required to be filtered or ranked. In these cases, exact tests are unavailable and the Welch's approximate test is most reliable one. The Welch's test involves two layers of approximations: approximating the distribution of the statistic by a t-distribution, which in turn depends on an approximate degrees of freedom...
March 15, 2019: Bioinformatics
Erica Giuliani, Maria Giovanna Desimio, Margherita Doria
The hexamethylene bisacetamide (HMBA) anticancer drug was dismissed due to limited efficacy in leukemic patients but it may re-enter into the clinics in HIV-1 eradication strategies because of its recently disclosed capacity to reactivate latent virus. Here, we investigated the impact of HMBA on the cytotoxicity of natural killer (NK) cells against acute T lymphoblastic leukemia (T-ALL) cells or HIV-1-infected T cells that exit from latency. We show that in T-ALL cells HMBA upmodulated MICB and ULBP2 ligands for the NKG2D activating receptor...
March 13, 2019: Scientific Reports
Chiara Borga, John Kimble Frazer
No abstract text is available yet for this article.
February 2019: International Journal of Hematologic Oncology
Nishit Gupta, Ravikiran Pawar, Sambhunath Banerjee, Subhajit Brahma, Asish Rath, Sundar Shewale, Mayur Parihar, Manish Singh, S R Arun, Shekhar Krishnan, Arpita Bhatacharyya, Anirban Das, Jeevan Kumar, Saurabh Bhave, Vivek Radhakrishnan, Reena Nair, Mammen Chandy, Neeraj Arora, Deepak Mishra
Background: For diagnosis, sub-categorization and follow up of Acute Leukemia (AL), phenotypic analysis using flow cytometry is mandatory. Material and methods: We retrospectively analyzed immunophenotypic data along with cytogenetics/molecular genetics data (wherever available) from 631 consecutive cases of AL diagnosed at our flow cytometry laboratory from January 2014 to August 2017. Results: Of the total 631 cases, 52.9% (n=334) were acute lymphoblastic leukemia (ALL), 43...
2019: Mediterranean Journal of Hematology and Infectious Diseases
H Pfeifer, G Cazzaniga, V H J van der Velden, J M Cayuela, B Schäfer, O Spinelli, S Akiki, S Avigad, I Bendit, K Borg, H Cavé, L Elia, S C Reshmi, G Gerrard, S Hayette, M Hermanson, A Juh, T Jurcek, M C Chillón, C Homburg, G Martinelli, V Kairisto, T Lange, T Lion, M C Mueller, F Pane, L Rai, C Damm-Welk, T Sacha, S Schnittger, T Touloumenidou, H Valerhaugen, P Vandenberghe, J Zuna, H Serve, E Herrmann, S Markovic, J J M van Dongen, O G Ottmann
Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation...
March 11, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jessica Burroughs-Garcia, Ameera Hasan, Gilseung Park, Chiara Borga, J Kimble Frazer
Zebrafish (Danio rerio) are a powerful model to study lymphocyte development. Like mammals, D. rerio possess an adaptive immune system that includes B and T lymphocytes. Studies of zebrafish lymphopoiesis are difficult because antibodies recognizing D. rerio cell surface markers are generally not available, complicating isolation and characterization of different lymphocyte populations, including B-lineage cells. Transgenic lines with lineage-specific fluorophore expression are often used to circumvent this challenge...
February 22, 2019: Journal of Visualized Experiments: JoVE
Padma Akkapeddi, Rita Fragoso, Julie A Hixon, Ana Sofia Ramalho, Mariana L Oliveira, Tânia Carvalho, Andreas Gloger, Mattia Matasci, Francisco Corzana, Scott K Durum, Dario Neri, Gonçalo J L Bernardes, João T Barata
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer for which treatment options often result in incomplete therapeutic efficacy and long-term side-effects. Interleukin 7 (IL-7) and its receptor IL-7Rα promote T-ALL development and mutational activation of IL-7Rα associates with very high risk in relapsed disease. Using combinatorial phage-display libraries and antibody reformatting, we generated a fully human IgG1 monoclonal antibody (named B12) against both wild-type and mutant human IL-7Rα, predicted to form a stable complex with IL-7Rα at a different site from IL-7...
March 8, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Iris Mattos Santos-Pirath, Laura Otto Walter, Mariana Franzoni Maioral, Patricia Devantier Neuenfeldt, Ricardo José Nunes, Maria Cláudia Santos-Silva
T-cell Acute Lymphoblastic Leukemia is an aggressive hematological malignancy originating from the malignant transformation of progenitor T cells at different stages of development. The treatment causes severe adverse effects and is associated with relapses and high morbidity and mortality rates. The present study aimed to evaluate the cytotoxic activity of 28 new compounds containing 3,4,5-trimethoxyphenyl analogues on hematological neoplastic cells lines. Cytotoxicity screening by the MTT method revealed that compound 1d was the most promising...
March 8, 2019: Biochemistry and Cell Biology
Andrew M Stein, Stephan A Grupp, John E Levine, Theodore W Laetsch, Michael A Pulsipher, Michael W Boyer, Keith J August, Bruce L Levine, Lori Tomassian, Sweta Shah, Mimi Leung, Pai-Hsi Huang, Rakesh Awasthi, Karen Thudium Mueller, Patricia A Wood, Carl H June
Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19+ B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion...
March 7, 2019: CPT: Pharmacometrics & Systems Pharmacology
Anna Richter, Catrin Roolf, Mohamed Hamed, Yvonne Saara Gladbach, Sina Sender, Christoph Konkolefski, Gudrun Knübel, Anett Sekora, Georg Fuellen, Brigitte Vollmar, Hugo Murua Escobar, Christian Junghanss
BACKGROUND: The tumor suppressor protein phosphatase and tensin homolog (PTEN) is a key regulator of the PI3K/AKT pathway which is frequently altered in a variety of tumors including a subset of acute B-lymphoblastic leukemias (B-ALL). While PTEN mutations and deletions are rare in B-ALL, promoter hypermethylation and posttranslational modifications are the main pathways of PTEN inactivation. Casein Kinase II (CK2) is often upregulated in B-ALL and phosphorylates both PTEN and DNA methyltransferase 3A, resulting in increased PI3K/AKT signaling and offering a potential mechanism for further regulation of tumor-related pathways...
March 6, 2019: BMC Cancer
Jacob T Nearing, Jessica Connors, Scott Whitehouse, Johan Van Limbergen, Tamara Macdonald, Ketan Kulkarni, Morgan G I Langille
Acute lymphoblastic leukemia is the most common pediatric cancer. Fortunately, survival rates exceed 90%, however, infectious complications remain a significant issue that can cause reductions in the quality of life and prognosis of patients. Recently, numerous studies have linked shifts in the gut microbiome composition to infection events in various hematological malignances including acute lymphoblastic leukemia (ALL). These studies have been limited to observing broad taxonomic changes using 16S rRNA gene profiling, while missing possible differences within microbial functions encoded by individual species...
2019: Frontiers in Cellular and Infection Microbiology
Xue-Yi Yang, Ye Sheng
Although miR-101 is involved in the development and progression of T-cell acute lymphoblastic leukemia (T-ALL), the underlying molecular mechanisms remain unclear. In this paper, we reported that miR-101 expression was inversely correlated with CX chemokine receptor 7 (CXCR7) level in T-ALL. Introducing miR-101 inhibited T-ALL cell proliferation and invasion in vitro and suppressed tumor growth and lung metastasis in vivo. CXCR7 was identified as a direct target of miR-101. The inhibitory effects of miR-101 were mimicked and counteracted by CXCR7 depletion and overexpression, respectively...
March 5, 2019: Oncology Research
Kshitij Verma, Tianzhu Zang, Trevor M Penning, Paul C Trippier
Aldo-keto reductase 1C3 (AKR1C3) catalyzes the synthesis of 9α,11β-prostaglandin (PG) F2α and PGF2α prostanoids that sustain the growth of myeloid precursors in the bone marrow. The enzyme is overexpressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). Moreover, AKR1C3 confers chemotherapeutic resistance to the anthracyclines; first-line agents for the treatment of leukemias. The highly homologous isoforms AKR1C1 and AKR1C2 inactive 5-dihydroprogesterone and their inhibition would be undesirable...
March 5, 2019: Journal of Medicinal Chemistry
Gina Ma, Jiaqi Shen, Kevin Pinz, Masayuki Wada, Jino Park, Soojin Kim, Tomiteru Togano, William Tse
T cell malignancies are aggressive diseases with no standard treatment available, often resulting in poor patient outcomes. Lately, the recent FDA approval of a CD19 CAR T cell therapy for B cell acute lymphoblastic leukemia has earned nationwide attention, leading to the possibility that success of CD19 CAR therapy can be extended to T cell malignancies. However, the impact of T cell depletion due to a shared antigen pool remains an issue to be resolved. Here, we describe a CD4CAR capable of eliminating CD4-positive T cell acute lymphoblastic leukemia in a systemic mouse model, with CAMPATH (alemtuzumab) as a natural safety switch to deplete the infused CD4CAR T cells to prevent toxicities associated with CD4 cell aplasia...
March 2, 2019: Stem Cell Reviews
Jong Bok Lee, Branson Chen, Daniel Vasic, Arjun D Law, Li Zhang
Significant improvements in the survival of patients with hematological cancers following hematopoietic stem cell transplantation provide evidence supporting the potency of immune cell-mediated anti-leukemic effects. Studies focusing on immune cell-based cancer therapies have made significant breakthroughs in the last few years. Adoptive cellular therapy (ACT), and chimeric antigen receptor (CAR) T cell therapy, in particular, has significantly increased the survival of patients with B cell acute lymphoblastic leukemia and aggressive B cell lymphoma...
February 23, 2019: Blood Reviews
Rahat-Ul-Ain Kashif, Mahwish Faizan, Saadia Anwar
OBJECTIVE: To describe the clinical spectrum and outcome-associated variables of pediatric malignant mediastinal masses in a resource-limited setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatric Hematology-Oncology, The Children's Hospital, Lahore, from October 2016 to November 2017. METHODOLOGY: Children with malignant mediastinal masses were enrolled. The variables studied were median age at presentation, gender distribution, immunisation status, socio-economic background, causes of delayed presentation, presenting complaints, complications of disease, methods for mass biopsy, final diagnosis, staging, and outcome of the disease...
March 2019: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Shanthi Sabarimurugan, Madhav Madurantakam Royam, Chellan Kumarasamy, Gothandam Kodiveri Muthukaliannan, Suja Samiappan, Rama Jayaraj
BACKGROUND: The prognostic value of microRNA (miRNA) expression in T-cell acute lymphoblastic leukemia (T-ALL) has generated significant research interest in recent years. However, most diagnostic and prognostic studies with regards to miRNA expression have been focused on combined B cell and T cell lymphoblastic leukemia. There are very few studies reporting the prognostic effects of miRNA expression on T-ALL. Therefore, a pioneer systematic review and meta-analysis was proposed to explore the possibilities of miRNAs as viable prognostic markers in T-ALL...
March 2019: Medicine (Baltimore)
Moshe Yeshurun, Daniel Weisdorf, Jacob M Rowe, Martin S Tallman, Mei-Jie Zhang, Hai-Lin Wang, Wael Saber, Marcos de Lima, Brenda M Sandmaier, Geoffrey Uy, Rammurti T Kamble, Mitchell S Cairo, Brenda W Cooper, Jean-Yves Cahn, Siddhartha Ganguly, Bruce Camitta, Leo F Verdonck, Christopher Dandoy, Miguel Angel Diaz, Bipin N Savani, Biju George, Jane Liesveld, Joseph McGuirk, Michael Byrne, Michael R Grunwald, William R Drobyski, Michael A Pulsipher, Hisham Abdel-Azim, Tim Prestidge, Matthew J Wieduwilt, Rodrigo Martino, Maxim Norkin, Amer Beitinjaneh, Sachiko Seo, Taiga Nishihori, Baldeep Wirk, Haydar Frangoul, Asad Bashey, Shahram Mori, David I Marks, Veronika Bachanova
Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL...
February 26, 2019: Blood Advances
Philipp Karschnia, Justin T Jordan, Deborah A Forst, Isabel C Arrillaga-Romany, Tracy T Batchelor, Joachim M Baehring, Nathan F Clement, L Nicolas Gonzalez Castro, Aline Herlopian, Marcela V Maus, Michaela H Schwaiblmair, Jacob D Soumerai, Ronald W Takvorian, Ephraim P Hochberg, Jeffrey A Barnes, Jeremy S Abramson, Matthew J Frigault, Jorg Dietrich
Chimeric antigen receptor (CAR) T-cells have emerged as a promising class of cell-based immunotherapy in refractory malignancies. Neurotoxicity represents a common and potentially life-threatening adverse effect of CAR T-cells, and clinical experience is limited. Here, we describe the clinical presentation and management of 25 adult patients who presented with neurotoxic syndromes after CAR T-cell therapy at the Massachusetts General Hospital. This cohort includes 24 patients treated with CD19-directed CAR T-cells for non-Hodgkin lymphoma (n=23) and acute lymphoblastic leukemia (n=1), and one patient treated with AFP-directed CAR T-cells for hepatocellular carcinoma (n=1)...
February 26, 2019: Blood
N Esiashvili, X Lu, K Ulin, F Laurie, S Kessel, J A Kalapurakal, T E Merchant, D S Followill, V Sathiaseelan, M K Schmitter, Meenakshi Devidas, Yichen Chen, D A Wall, P A Brown, S P Hunger, S A Grupp, M A Pulsipher
PURPOSE: To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) on Children's Oncology Group (COG) trial. PATIENTS AND METHODS: TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens; allowing institutional flexibility regarding TBI techniques, including lung shielding...
February 23, 2019: International Journal of Radiation Oncology, Biology, Physics
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