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childhood acute lymphoblastic leukemia

Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
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
Łukasz Sędek, Prisca Theunissen, Elaine Sobral da Costa, Alita van der Sluijs-Gelling, Ester Mejstrikova, Giuseppe Gaipa, Alicja Sonsala, Magdalena Twardoch, Elen Oliveira, Michaela Novakova, Chiara Buracchi, Jacques J M van Dongen, Alberto Orfao, Vincent H J van der Velden, Tomasz Szczepański
BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values...
March 9, 2018: Journal of Immunological Methods
Dmitrijs Rots, Madara Kreile, Sergejs Nikulshin, Zhanna Kovalova, Linda Gailite
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Modern treatment protocols allow achievement of long-term event-free survival rates in up to 85% of cases, although the treatment response varies among different patient groups. It is hypothesized that treatment response is influenced by the IL15 gene variations, although research results are conflicting. To analyze IL15 gene variations influence treatment response, clinical course and the risk of developing ALL we performed a case-control and family-based study...
March 12, 2018: Pediatric Hematology and Oncology
Wei Liu, Yin Ting Cheung, Tara M Brinkman, Pia Banerjee, Deokumar Srivastava, Vikki G Nolan, Hongmei Zhang, James G Gurney, Ching-Hon Pui, Leslie L Robison, Melissa M Hudson, Kevin R Krull
BACKGROUND: Prevalence of emotional, behavioral and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia (ALL) treated on a chemotherapy-only protocol were not well defined. METHODS: Self- and parent-reported emotional and behavioral symptoms were assessed for 161 survivors of childhood ALL (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post-diagnosis). Age- and sex-adjusted scores were calculated for standardized measures, and compared to 90th percentile of norms...
March 9, 2018: Psycho-oncology
Rene Marke, Frank N van Leeuwen, Blanca Scheijen
Transcription factor IKZF1 (IKAROS) acts as a critical regulator of lymphoid differentiation and is frequently deleted or mutated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IKZF1 gene defects are associated with inferior treatment outcome in both childhood and adult BCP-ALL and occur in more than 70% of BCR-ABL1 positive and BCR-ABL1-like ALL cases. Over the past few years, much has been learned about the tumor suppressive function of IKZF1 during leukemia development and the molecular pathways that relate to its impact on treatment outcome...
March 8, 2018: Haematologica
Ida M Ki Moore, Kari M Koerner, Patricia M Gundy, David W Montgomery, Kathleen C Insel, Lynnette L Harris, Olga A Taylor, Marilyn J Hockenberry
Aggressive central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia (ALL), the most prevalent cancer among children and adolescents, prevents metastasis of leukemia cells into the brain. Up to 60% of survivors experience cognitive problems, but knowledge about risk factors for and mechanisms of neurologic injury is lacking. Objectives of the present study were to (1) quantify changes in oxidant defense and apoptosis over the course of ALL therapy and (2) elucidate risk factors for long-term cognitive problems...
January 1, 2018: Biological Research for Nursing
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
Wei Liu, Yin Ting Cheung, Heather M Conklin, Lisa M Jacola, DeoKumar Srivastava, Vikki G Nolan, Hongmei Zhang, James G Gurney, I-Chan Huang, Leslie L Robison, Ching-Hon Pui, Melissa M Hudson, Kevin R Krull
PURPOSE: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. METHODS: We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected...
February 27, 2018: Journal of Cancer Survivorship: Research and Practice
Sumit Gupta, Meenakshi Devidas, Mignon L Loh, Elizabeth A Raetz, Si Chen, Cindy Wang, Patrick Brown, Andrew J Carroll, Nyla A Heerema, Julie M Gastier-Foster, Kimberly P Dunsmore, Eric C Larsen, Kelly W Maloney, Leonard A Mattano, Stuart S Winter, Naomi J Winick, William L Carroll, Stephen P Hunger, Michael J Borowitz, Brent L Wood
Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs. flow cytometry using patients age 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N = 9350)...
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Maitane Umerez, Susana Garcia-Obregon, Idoia Martin-Guerrero, Itziar Astigarraga, Angela Gutierrez-Camino, Africa Garcia-Orad
Childhood acute lymphoblastic leukemia survival rates have increased remarkably during last decades due, in part, to intensive treatment protocols. However, therapy resistance and toxicity are still two important barriers to survival. In this context, pharmacoepigenetics arises as a tool to identify new predictive markers, required to guide clinicians on risk stratification and dose individualization. The present study reviews current evidence about miRNA implication on childhood acute lymphoblastic leukemia therapy resistance and toxicity...
February 22, 2018: Pharmacogenomics
Ninna Brix, Henrik Hasle, Steen Rosthøj, Troels Herlin
Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasia and may present with arthralgia and arthritis, with the risk of misdiagnosis and diagnostic delay. We describe in detail arthropathy (arthritis/arthralgia) among children with leukemia as the children's laboratory results, misdiagnosis, and treatment before the diagnosis of ALL and the diagnostic delay. In this retrospective cohort study, we reviewed records of 286 children aged 1-15 years diagnosed with ALL from January 1992 to March 2013...
February 21, 2018: Clinical Rheumatology
Menha Swellam, Maha Hashim, Magda Sayed Mahmoud, Amal Ramadan, Naglaa M Hassan
Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer commonly affecting children due to dysregulation of miRNA expression. In the current study, authors investigated the expression profile for miRNA-125b-1 and miRNA-203 among childhood ALL. Blood samples were collected from newly diagnosed childhood ALL and healthy control children. The expression profile for candidate miRNAs was detected using quantitative RT-PCR analysis. Statistical analysis were performed using receiver operating characteristic curve (ROC) to examine the diagnostic efficacy of the two miRNA and their levels among ALL clinicopathological factors and phenotypes...
February 19, 2018: Biochemical Genetics
Xue Li, Dong Li, Xiaoyang Huang, Panpan Zhou, Qing Shi, Bing Zhang, Xiuli Ju
Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs...
February 14, 2018: Leukemia Research
Paul B Sinclair, Helen H Blair, Sarra L Ryan, Lars Buechler, Joanna Cheng, Jake Clayton, Rebecca Hanna, Shaun Hollern, Zoe Hawking, Matthew Bashton, Claire J Schwab, Lisa Jones, Lisa J Russell, Helen Marr, Peter Carey, Christina Halsey, Olaf Heidenreich, Anthony V Moorman, Christine J Harrison
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the central nervous system...
February 15, 2018: Haematologica
Manisha Agarwal, Sameer Bakhshi, Sadanand N Dwivedi, Madhulika Kabra, Rashmi Shukla, Rachna Seth
BACKGROUND: Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) genes are implicated in many malignancies including acute lymphoblastic leukemia (ALL). These tumor suppressor genes, with a key regulatory role in cell cycle are located on chromosome 9p21.3. Previous studies involving CDKN2A/B gene deletions have shown mixed associations with survival outcome in childhood ALL. PROCEDURE: Hundred and four newly diagnosed children with ALL (1-14 years) were enrolled in this study...
February 15, 2018: Pediatric Blood & Cancer
Gholamreza Bahari, Mohammad Hashemi, Majid Naderi, Simin Sadeghi-Bojd, Mohsen Taheri
The present case-control study was conducted on 110 children with acute lymphoblastic leukemia (ALL) and 120 healthy children to determine the impact of polymorphisms in paired-box gene 8 (PAX8) antisense RNA 1 (PAX8-AS1), namely rs4848320 C>T, rs6726151 T>G and rs1110839 G>T, on ALL risk. Genotyping was performed through the polymerase chain reaction-restriction fragment length polymorphism method. The findings indicated that the rs4848320 variant increased the risk of ALL in codominant [CT vs. CC: odds ratio (OR)=2...
February 2018: Biomedical Reports
Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Aleš Hnízda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J Yang, Xiaofan Zhu, Xin Liu
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) comprises of approximately 10-15% of childhood ALL cases, many of whom respond exquisitely to tyrosine kinase inhibitors (TKIs), e.g., imatinib in PDGFRB -rearranged ALL. However, some cases developed drug resistance to TKIs with mechanisms poorly understood. In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB , and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation PDGFRBC843G , which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib...
February 6, 2018: Blood
D S Lima, R P G Lemes, D M Matos
In tumor microenvironment, immunosuppression is a common event and results from the inhibition of activated immune cells and generation of cells with immunosuppressive capacity, as some subtypes of monocytes. The aim of this study was to evaluate the presence of immunosuppressive CD14 + /HLA-DR low/- monocytes in pediatric patients with the diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) and, moreover, verify whether the chemotherapeutic treatment has any effect on these cells. Peripheral blood (PB) and bone marrow (BM) samples were collected from 15 untreated pediatric patients...
February 10, 2018: Medical Oncology
Olga Zając-Spychała, Mikolaj Pawlak, Katarzyna Karmelita-Katulska, Jakub Pilarczyk, Katarzyna Jończyk-Potoczna, Agnieszka Przepióra, Katarzyna Derwich, Jacek Wachowiak
The aim of the study was to evaluate the long-term neurodevelopmental consequences of currently applied acute lymphoblastic leukemia (ALL) therapy containing chemotherapy alone or combined with 12 Gy radiotherapy. Seventy-nine children aged 6.3-21.7 years diagnosed with ALL and treated according to ALL IC-BFM 2002 have been studied. The control group consisted of 23 children newly diagnosed with ALL. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between three therapeutic schemes and patients prior to treatment...
February 9, 2018: Leukemia & Lymphoma
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