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acute lymphoblastic leukemia -L3 type

Aleš Hnízda, Milan Fábry, Takaya Moriyama, Petr Pachl, Michael Kugler, Vítězslav Brinsa, David B Ascher, William L Carroll, Petr Novák, Markéta Žaliová, Jan Trka, Pavlína Řezáčová, Jun J Yang, Václav Veverka
Activating mutations in NT5C2, a gene encoding cytosolic purine 5'-nucleotidase (cN-II), confer chemoresistance in relapsed acute lymphoblastic leukemia. Here we show that all mutants became independent of allosteric effects of ATP and thus constitutively active. Structural mapping of mutations described in patients demonstrates that 90% of leukemia-specific allelles directly affect two regulatory hotspots within the cN-II molecule-the helix A region: residues 355-365, and the intersubunit interface: helix B (232-242) and flexible interhelical loop L (400-418)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Elva Jiménez-Hernández, Arturo Fajardo-Gutiérrez, Juan Carlos Núñez-Enriquez, Jorge Alfonso Martín-Trejo, Laura Eugenia Espinoza-Hernández, Janet Flores-Lujano, José Arellano-Galindo, Aurora Medina-Sanson, Rogelio Paredes-Aguilera, Laura Elizabeth Merino-Pasaye, Martha Margarita Velázquez-Aviña, José Refugio Torres-Nava, Rosa Martha Espinosa-Elizondo, Raquel Amador-Sánchez, Juan José Dosta-Herrera, Javier Anastacio Mondragón-García, Heriberto Valdés-Guzmán, Laura Mejía-Pérez, Gilberto Espinoza-Anrubio, María Minerva Paz-Bribiesca, Perla Salcedo-Lozada, Rodolfo Ángel Landa-García, Rosario Ramírez-Colorado, Luis Hernández-Mora, María Luisa Pérez-Saldivar, Marlene Santamaría-Ascencio, Anselmo López-Loyola, Arturo Hermilo Godoy-Esquivel, Luis Ramiro García-López, Alison Ireri Anguiano-Ávalos, Karina Mora-Rico, Alejandro Castañeda-Echevarría, Roberto Rodríguez-Jiménez, José Alberto Cibrian-Cruz, Karina Anastacia Solís-Labastida, Rocío Cárdenas-Cardos, Armando Martínez-Avalos, Luz Victoria Flores-Villegas, José Gabriel Peñaloza-González, Ana Itamar González-Ávila, Martha Beatriz Altamirano-García, Norma López-Santiago, Martin Sánchez-Ruiz, Roberto Rivera-Luna, Luis Rodolfo Rodríguez-Villalobos, Francisco Hernández-Pérez, Jaime Ángel Olvera-Durán, Luis Rey García-Cortés, Minerva Mata-Rocha, Omar Alejandro Sepúlveda-Robles, Cesar Raúl González-Bonilla, Vilma Carolina Bekker-Méndez, Silvia Jiménez-Morales, Haydee Rosas-Vargas, Juan Manuel Mejía-Aranguré
In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015...
March 13, 2018: Cancer Medicine
P Dallé Rosa, M Ramirez-Castrillon, P Valente, A Meneghello Fuentefria, A D Van Diepeningen, L Z Goldani
Invasive fusariosis has a high mortality and is predominantly observed in patients with leukemia. We report the first case of a novel species of Fusarium, Fusarium riograndense sp. nov, isolated from a lesion in the nasal cavity lesion of a patient with acute lymphoblastic leukemia. The etiological agent was identified by Multilocus Sequencing Typing (MLST), including RPB2, TEF-1α, and ITS-LSU sequences, the gold standard technique to identify new species of Fusarium. MLST and phenotypic data strongly supported its inclusion in the F...
March 7, 2018: Journal de Mycologie Médicale
E Delvin, N Alos, F Rauch, V Marcil, S Morel, M Boisvert, M-A Lecours, C Laverdière, D Sinnett, M Krajinovic, J Dubois, S Drouin, G Lefebvre, M Samoilenko, C Nyalendo, E Cavalier, E Levy
BACKGROUND: The remarkable progress in the treatment of childhood acute lymphoblastic leukemia (cALL) has led to a survival rate reaching 90%. This success story is unfortunately linked to increased risk of impaired skeletal mass accumulation during childhood and adolescence, predisposing the patients to osteoporosis and pathological fractures at adulthood. OBJECTIVE: This study aims at characterizing the vitamin D status and bone health biomarkers in a well-characterized cohort of cALL survivors...
February 21, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Alberto Martín-Lorenzo, Franziska Auer, Lai N Chan, Idoia García-Ramírez, Ines Gonzalez-Herrero, Guillermo Rodríguez-Hernández, Christoph Bartenhagen, Martin Dugas, Michael Gombert, Sebastian Ginzel, Oscar Blanco, Alberto Orfao, Diego Alonso-López, Javier De Las Rivas, Maria Begoña García-Cenador, Francisco Javier García Criado, Markus Müschen, Isidro Sánchez-García, Arndt Borkhardt, Carolina Vicente-Dueñas, Julia Hauer
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease...
February 28, 2018: Cancer Research
Alexey Teplyakov, Galina Obmolova, Jinquan Luo, Gary L Gilliland
CD19 is a transmembrane protein expressed on malignant B cells, but not in other lineages or other tissues, which makes it an attractive target for monoclonal antibody-mediated immunotherapy. Anti-CD19 antibody B43 was utilized in a bispecific T-cell engager (BiTE) blinatumomab, that demonstrated potency for the treatment of relapsed acute lymphoblastic leukemia. To gain insight into the mechanism of action of the antibody, the crystal structure of B43 Fab was determined in complex with CD19 and in the unbound form...
February 28, 2018: Proteins
Qi Zhang, Ce Shi, Lina Han, Nitin Jain, Kathryn G Roberts, Helen Ma, Tianyu Cai, Antonio Cavazos, Yoko Tabe, Rodrigo O Jacamo, Hong Mu, Yang Zhao, Jing Wang, Shuo-Chieh Wu, Fenglin Cao, Zhihong Zeng, Jin Zhou, Yingchang Mi, Elias J Jabbour, Ross Levine, Sarah K Tasian, Charles G Mullighan, David M Weinstock, David A Fruman, Marina Konopleva
Patients with cytokine receptor-like factor 2 rearranged ( CRLF2 -re) subgroup Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like B-ALL) have a high relapse rate and poor clinical outcomes. CRFL2 -re Ph-like B-ALL is characterized by heightened activation of multiple signaling pathways, including the JAK/STAT and PI3K/AKT/mTOR pathways. We hypothesized that the combined inhibition by JAK2 and mTOR inhibitors would induce an additive antileukemia effect in CRLF2 -re Ph-like B-ALL. In this study, we tested the antileukemia efficacy of the type I JAK inhibitor ruxolitinib and type II JAK inhibitor NVP-BBT594 (hereafter abbreviated BBT594) [1] alone and combined with allosteric mTOR inhibitor rapamycin and a second generation ATP-competitive mTOR kinase inhibitor AZD2014...
January 30, 2018: Oncotarget
Megan Romeo, Tetiana Hutchison, Aditi Malu, Averi White, Janice Kim, Rachel Gardner, Katie Smith, Katherine Nelson, Rachel Bergeson, Ryan McKee, Carolyn Harrod, Lee Ratner, Bernhard Lüscher, Ernest Martinez, Robert Harrod
In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression...
February 17, 2018: Virology
Nivedita Patni, Xilong Li, Beverley Adams-Huet, Abhimanyu Garg
BACKGROUND: Extreme hypertriglyceridemia (eHTG; serum triglycerides ≥ 2000 mg/dL) poses a significant risk for acute pancreatitis. There is paucity of data regarding the prevalence and etiology of eHTG in children. OBJECTIVE: To determine the prevalence, clinical features and etiologies of patients with eHTG at a tertiary children's hospital in the United States and in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: A retrospective analysis was conducted of the electronic medical records of the Children's Medical Center, Dallas, from 2000-2015, and the NHANES data from 2005-2014 for eHTG...
January 12, 2018: Journal of Clinical Lipidology
Habibe Kurt, Lan Zheng, Hagop M Kantarjian, Guilin Tang, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zimu Gong, Hesham M Amin, Sergej N Konoplev, Mark J Routbort, Xin Han, Wei Wang, L Jeffery Medeiros, Shimin Hu
The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis...
February 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Vicki Xie, Daochen Tong, Craig T Wallington-Beddoe, Ken F Bradstock, Linda J Bendall
Background: Sphingosine kinase (SphK) 2 has been implicated in the development of a range of cancers and inhibitors of this enzyme are currently in clinical trial. We have previously demonstrated a role for SphK2 in the development of acute lymphoblastic leukemia (ALL). Methods: In this and our previous study we use mouse models: in the previous study the disease was driven by the proto-oncogene BCR/ABL1, while in this study cancer risk was elevated by deletion of the tumor suppressor ARF...
2018: Biomarker Research
Hiroki Miura, Fumihiko Hattori, Hidetoshi Uchida, Tadayoshi Hata, Kazuko Kudo, Masatoki Sato, Tetsushi Yoshikawa
BACKGROUND: Respiratory syncytial virus (RSV) infection is common and may be severe among patients with preexisting cardiac anomalies, but direct involvement of myocardial damage is not common in those patients. Additionally, myocardial involvement has been rarely described among immune compromised children. CASE PRESENTATION: A 4-year-old girl with acute lymphoblastic leukemia who received maintenance chemotherapy in an outpatient clinic developed systemic inflammatory response syndrome...
February 12, 2018: BMC Pediatrics
Rui Chen, Zhihui Deng
OBJECTIVE To assess the association of polymorphisms of KIR2DL4 gene with leukemia among ethnic Hans from southern China. METHODS A total of 590 leukemia patients were recruited, which included 283 cases of acute lymphoblastic leukemia (ALL), 277 cases of acute myeloid leukemia (AML), and 80 cases of chronic myeloid leukemia (CML). Meanwhile, 306 healthy controls were randomly selected from volunteer blood donors. Both groups were subjected to sequence-based typing of the entire coding sequence of the KIR2DL4 gene using an in-house assay...
February 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Zengkai Pan, Min Yang, Kezhi Huang, Guntram Büsche, Silke Glage, Arnold Ganser, Zhixiong Li
Immunophenotypic analysis using multiparameter flow cytometry is an indispensable tool for diagnosis and management of acute leukemia. Mouse models have been widely used for medical research for more than 100 years and are indispensable for leukemia research. However, immunophenotypic analysis of murine leukemia was not always performed in published studies, and blast gating for isolation of blasts was shown only in very few studies. No systemic characterization of all types of murine acute leukemia in large cohorts by flow cytometry has been reported...
January 5, 2018: Oncotarget
Roberta Di Blasi, Chiara Cattaneo, Russell E Lewis, Mario Tumbarello, Laura Angelici, Giulia Dragonetti, Alessandro Busca, Benedetta Cambò, Anna Candoni, Monica Cesarini, Simone Cesaro, Mario Delia, Rosa Fanci, Francesca Farina, Mariagrazia Garzia, Antonio Giordano, Bruno Martino, Lorella Melillo, Gianpaolo Nadali, Vincenzo Perriello, Marco Picardi, Angela Maria Quinto, Prassede Salutari, Angelica Spolzino, Adriana Vacca, Calogero Vetro, Michelle Zancanella, Annamaria Nosari, Franco Aversa, Livio Pagano
The purpose of the present study is to estimate the current incidence of febrile events (FEs) and infectious episodes in acute lymphoblastic leukemia (ALL) and evaluate the outcome. We analyzed data on all FEs in a cohort of patients affected by ALL admitted to 20 Italian hematologic centers during 21 months of observation from April 1, 2012 to December 31, 2013. Data about treatment phase, steroids, neutropenia, type and site of infection, and outcome of infection were collected. The population comprehended 271 ALL adult patients...
February 7, 2018: Annals of Hematology
Taotao Ling, Walter Lang, Xiang Feng, Sourav Das, Julie Maier, Cynthia Jeffries, Anang Shelat, Fatima Rivas
Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Up to a quarter of ALL patients relapse and face poor prognosis. To identify new compound leads, we conducted a phenotypic screen using terrestrial natural product (NP) fractions against immortalized ALL cellular models. We identified vitexin, a flavonoid, as a promising hit with biological activity (EC50 = 30 μM) in pre-B cell ALL models with no toxicity against normal human tissue (BJ cells) at the tested concentrations...
January 30, 2018: European Journal of Medicinal Chemistry
Prajwal C Boddu, Sa A Wang, Naveen Pemmaraju, Zhenya Tang, Shimin Hu, Shaoying Li, Jie Xu, L Jeffrey Medeiros, Guilin Tang
8q24/MYC rearrangements resulting in MYC overexpression occur most frequently in lymphoid neoplasms. MYC rearrangements rarely have been described in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Over an 8-year period in our hospital, 5 of 41 (12%) patients with BPDCN were shown 8q24/MYC rearrangements, including 2 with t(6;8)(p21;q24), 1 with t(8;14)(q24;q32), 1 with t(X;8)(q24;q24), and 1 with t(3;8)(p25;q24). 8q24/MYC rearrangement was present in the stemline in 4 patients and in the sideline in one; the latter was a patient with primary myelofibrosis who then developed BPDCN...
March 2018: Leukemia Research
Yuichiro Kojima, Yosuke Hirotsu, Wataru Omata, Makoto Sugimori, Shinya Takaoka, Hiroshi Ashizawa, Keiko Nakagomi, Dai Yoshimura, Kenji Hosoda, Yoji Suzuki, Hitoshi Mochizuki, Masao Omata
AIM: The single nucleotide polymorphism (SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease (IBD) treated with thiopurines. METHODS: Ninety-six Japanese patients with IBD were enrolled...
January 28, 2018: World Journal of Gastroenterology: WJG
Amer Abdulrahman Almaiman
Lymphoid (or lymphocytic/lymphoblastic) leukemia, one of two major types of leukemias (lymphoid and myeloid), is divided into two subtypes, acute lymphoid leukemia (ALL) and chronic lymphocytic leukemia (CLL), depending on the maturation stage and speed of multiplication of the bone marrow lymphocytes. Early diagnosis and treatment can make the difference between life and death. Advancements in the field of proteomics may allow the development of early biomarkers and more effective agents to combat both these types of cancer, and to better understand the underlying mechanisms of the disease...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Anita Vallacha, Ghulam Haider, Wiky Raja, Dinesh Kumar
OBJECTIVE: To determine the remission rate in adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Oncology, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January, 2016 to March, 2017. METHODOLOGY: Adolescent and young adult (AYA) patients aged 15-39 years, newly diagnosed with acute lymphoblastic leukemia from January, 2016 to March, 2017...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
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