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Acute lymphoid leukemia

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https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#1
Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Kirsten Bleckmann, Marie Trkova, Eliska Potuckova, Martina Vaskova, Jana Linhartova, Katerina Machova Polakova, Eva Fronkova, Walter Muskovic, Jodie E Giles, Peter J Shaw, Gunnar Cario, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, over 20% of children (25% [8/32] with minor and 12.5% [1/8] with Major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28306688/oxidative-stress-in-tunisian-patients-with-acute-lymphoblastic-leukemia-and-its-involvement-in-leukemic-relapse
#2
Lobna Ben Mahmoud, Moez Mdhaffar, Hanene Ghozzi, Mariam Ammar, Ahmed Hakim, Rim Atheymen, Zouheir Sahnoun, Moez Elloumi, Khaled Zeghal
The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy...
April 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28299658/clinical-relevance-of-runx1-and-cbfb-alterations-in-acute-myeloid-leukemia-and-other-hematological-disorders
#3
Klaus H Metzeler, Clara D Bloomfield
The translocation t(8;21), leading to a fusion between the RUNX1 gene and the RUNX1T1 locus, was the first chromosomal translocation identified in cancer. Since the first description of this balanced rearrangement in a patient with acute myeloid leukemia (AML) in 1973, RUNX1 translocations and point mutations have been found in various myeloid and lymphoid neoplasms. In this chapter, we summarize the currently available data on the clinical relevance of core binding factor gene alterations in hematological disorders...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28297628/genetic-basis-of-acute-lymphoblastic-leukemia
#4
Ilaria Iacobucci, Charles G Mullighan
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and despite cure rates exceeding 90% in children, it remains an important cause of morbidity and mortality in children and adults. The past decade has been marked by extraordinary advances into the genetic basis of leukemogenesis and treatment responsiveness in ALL. Both B-cell and T-cell ALL comprise multiple subtypes harboring distinct constellations of somatic structural DNA rearrangements and sequence mutations that commonly perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28260788/apobec-signature-mutation-generates-an-oncogenic-enhancer-that-drives-lmo1-expression-in-t-all
#5
Z Li, B J Abraham, A Berezovskaya, N Farah, Y Liu, T Leon, A Fielding, S H Tan, T Sanda, A S Weintraub, B Li, S Shen, J Zhang, M R Mansour, R A Young, A T Look
Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells resulting in clonal selection. Although most cancer causing mutations have been detected in the protein-coding regions of the cancer genome, driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention...
March 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28229399/neurological-complications-of-the-leukemias-across-the-ages
#6
REVIEW
Stephanie Berg, Sucha Nand
PURPOSE OF REVIEW: Acute and chronic leukemias are heterogeneous diseases and can affect any part of the body upon initial discovery. Understanding the sequela of systemic involvement is key for proper diagnosis and treatment. RECENT FINDINGS: Over the decades, new research has emerged regarding neurological complications of the myeloid or lymphoid leukemias. Central nervous system involvement usually confers a poor prognosis and requires emergent treatment. Standard of care still involves systemic therapy, intrathecal administration of chemotherapeutic agents, and cranial radiation...
February 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28224619/l-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#7
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#8
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n = 184), myelodysplastic syndrome (n = 69), acute lymphocytic leukemia (n = 57), chronic myelogenous leukemia (CML, n = 36), lymphoid neoplasms (n = 38), adult T cell leukemia/lymphoma (n = 18), and multiple myeloma (n = 12)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28218826/synthesis-and-antiproliferative-effect-of-ethyl-4-4-substitutedpiperidin-1-yl-benzylpyrrolo-1-2-a-quinoxaline-carboxylate-derivatives-on-human-leukemic-cells
#9
Jean Guillon, Vanessa Desplat, Marian Vincenzi, Romain Lucas, Stéphane Moreau, Solène Savrimoutou, Noel Pinaud, David Bigat, Elodie Enriquez, Mathieu Marchivie, Sylvain Routier, Pascal Sonnet, Filomena Rossi, Luisa Ronga
Acute leukemia is a hematological malignancy with high incidence and recurrence rates, and is characterized by an accumulation of blasts in bone marrow due to proliferation of immature lymphoid or myeloid cells associated with a blockade of differentiation. The heterogeneity of leukemia led to look for new specific molecules for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic derivatives that attracted attention due to their large spread biological activities, we have focused our interest towards the pyrrolo[1,2-a]quinoxaline heterocyclic framework that has been previously identified as an interesting scaffold for antiproliferative activities against various human cancer cell lines...
February 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28195090/mixed-phenotypic-acute-leukemia-series-from-tertiary-care-center
#10
Ravikiran N Pawar, Sambhunath Banerjee, Subhajit Bramha, Shekhar Krishnan, Arpita Bhattacharya, Vaskar Saha, Anupam Chakrapani, Saurabh Bhave, Mammen Chandy, Reena Nair, Mayur Parihar, Neeraj Arora, D K Mishra
INTRODUCTION: Mixed-phenotype acute leukemias (MPALs) are a heterogeneous group of rare leukemias constituting approximately 2%-5% of all leukemias, in which assigning a single lineage of origin is not possible. They are diagnosed by either the presence of antigens of more than one lineage or by the presence of dual population of blasts belonging to two or more lineages. We highlight the clinicopathological, immunophenotype, and genetic data of a cohort (n = 14) of patients diagnosed and treated at our center...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#11
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#12
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#13
Raman Sood, Yasuhiko Kamikubo, Paul Liu
RUNX1 is a member of the core binding factor family of transcription factors and is indispensable for the establishment of definitive hematopoiesis in vertebrates. RUNX1 is one of the most frequently mutated genes in a variety of hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with associated myeloid malignancies (FPDMM). Somatic mutations and chromosomal rearrangements involving RUNX1 are frequently observed in myelodysplastic syndrome (MDS) and leukemias of myeloid and lymphoid lineages, i...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28171800/epigenetic-drug-combination-overcomes-osteoblast-induced-chemoprotection-in-pediatric-acute-lymphoid-leukemia
#14
Anthony Quagliano, Anilkumar Gopalakrishnapillai, Sonali P Barwe
Although there has been much progress in the treatment of acute lymphoblastic leukemia (ALL), decreased sensitivity to chemotherapy remains a significant issue. Recent studies have shown how interactions with the bone marrow microenvironment can protect ALL cells from chemotherapy and allow for the persistence of the disease. Epigenetic drugs have been used for the treatment of ALL, but there are no reports on whether these drugs can overcome bone marrow-induced chemoprotection. Our study investigates the ability of the DNA methyltransferase inhibitor azacitidine and the histone deacetylase inhibitor panobinostat to overcome chemoprotective effects mediated by osteoblasts...
January 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28151996/nkl-homeobox-gene-activities-in-hematopoietic-stem-cells-t-cell-development-and-t-cell-leukemia
#15
Stefan Nagel, Claudia Pommerenke, Michaela Scherr, Corinna Meyer, Maren Kaufmann, Karin Battmer, Roderick A F MacLeod, Hans G Drexler
T-cell acute lymphoblastic leukemia (T-ALL) cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs) and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1) and three in common lymphoid progenitors (HHEX, HLX1 and MSX1)...
2017: PloS One
https://www.readbyqxmd.com/read/28150907/venous-thromboembolism-following-l-asparaginase-treatment-for-lymphoid-malignancies-in-korea
#16
J H Lee, J Lee, H-Y Yhim, D Oh, S-M Bang
Essentials Data on venous thromboembolism (VTE) after L-asparaginase (L-asp) in Asian lymphoma are scarce. This is a population-based study in Asian patients with lymphoid disease and L-asp-related VTE. The overall incidence of L-asp-associated VTE was similar to reports on Caucasians. This first and largest study in Asians shows that mainly adult patients are at risk of thrombosis. SUMMARY: Background L-asparaginase (L-asp)-associated venous thromboembolism (VTE) is a serious adverse complication associated with acute lymphoblastic leukemia (ALL) and lymphoma treatment...
February 2, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28134942/impact-of-aberrant-antigens-in-the-outcome-of-patients-with-acute-leukemia-at-a-referral-institution-in-mexico-city
#17
Sergio Rodríguez-Rodríguez, Alan Pomerantz, Roberta Demichelis-Gómez, Georgina Barrera-Lumbreras, Olga V Barrales-Benítez, Xavier Lopez-Karpovitch, Álvaro Aguayo
BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29...
November 2016: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
https://www.readbyqxmd.com/read/28126143/-copy-number-alterations-in-adult-patients-with-mature-b-acute-lymphoblastic-leukemia-treated-with-specific-immunochemotherapy
#18
Jordi Ribera, Lurdes Zamora, Olga García, Jesús-María Hernández-Rivas, Eulàlia Genescà, Josep-Maria Ribera
BACKGROUND AND OBJECTIVE: Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. PATIENTS AND METHODS: We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy...
December 2, 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28123246/flow-cytometric-detection-of-minimal-residual-disease-in-b-lineage-acute-lymphoblastic-leukemia-by-using-mrd-lite-panel
#19
Tathagata Chatterjee, Venkatesan Somasundaram
BACKGROUND: Normal B lymphoid precursors that express CD19, CD10, and/or CD34 are highly sensitive to corticosteroids and after two weeks of remission-induction therapy, they form less than 0.01% of the bone marrow population. More than 0.01% of such cells indicate minimal residual disease (MRD). MRD "lite" panel uses only three antibodies, namely CD19, CD10, and CD34 for MRD detection in cases of B-lineage acute lymphoblastic leukemia (B-ALL) expressing CD19, CD10, and/or CD34 by flow cytometry...
January 2017: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28123174/new-diagnosis-of-atypical-ataxia-telangiectasia-in-a-17-year-old-boy-with-t-cell-acute-lymphoblastic-leukemia-and-a-novel-atm-mutation
#20
Jasmin Roohi, Jennifer Crowe, Denis Loredan, Kwame Anyane-Yeboa, Mahesh M Mansukhani, Lenore Omesi, Jennifer Levine, Anya Revah Politi, Shan Zha
Ataxia-telangiectasia (A-T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM gene. Typically, it presents in early childhood with progressive cerebellar dysfunction along with immunodeficiency and oculocutaneous telangiectasia. An increased risk of malignancy is also associated with the syndrome and, rarely, may be the presenting feature in small children. We describe a 17-year-old boy with slurred speech, mild motor delays and learning disability diagnosed with atypical A-T in the setting of T-cell acute lymphoblastic leukemia...
January 26, 2017: Journal of Human Genetics
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