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Acute lymphoid leukemia

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https://www.readbyqxmd.com/read/28521633/cd30-expression-in-pediatric-neoplasms-study-of-585-cases
#1
Jinjun Cheng, Haiqing Zhu, John Kim Choi
CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8), and its normal expression is restricted to activated T and B cells. In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody. CD30 expression has been reported also in mostly adult non-lymphoid malignancies, raising the possibility of CD30-targeted therapy for additional tumors. In this study, we examined the incidence of CD30 expression in 251 hematopoietic and 334 non-hematopoietic cases of pediatric tumors...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28508352/pediatric-precursor-b-acute-lymphoblastic-leukemia-are-t-helper-cells-the-missing-link-in-the-infectious-etiology-theory
#2
REVIEW
Simone Bürgler, David Nadal
Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28498310/selective-expression-of-flt3-within-the-mouse-hematopoietic-stem-cell-compartment
#3
Ciaran James Mooney, Alan Cunningham, Panagiotis Tsapogas, Kai-Michael Toellner, Geoffrey Brown
The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating mutations are commonly present in acute myeloid and lymphoid leukemias. These findings underscore the importance of Flt3 to steady-state and malignant hematopoiesis. In this study, the expression of Flt3 protein and Flt3 mRNA by single cells within the hematopoietic stem cell (HSC) and HPC bone marrow compartments of C57/BL6 mice was investigated using flow cytometry and the quantitative reverse transcription polymerase chain reaction...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28482851/checkpoint-inhibitors-in-hematological-malignancies
#4
REVIEW
Chi Young Ok, Ken H Young
Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data support that their functions are dysregulated in lymphoid neoplasms, including plasma cell myeloma, myelodysplastic syndrome, and acute myeloid leukemia. In lymphoid neoplasms, aberrations in 9p24.1 (PD-L1, PD-L2, and JAK2 locus), latent Epstein-Barr virus infection, PD-L1 3'-untranslated region disruption, and constitutive JAK-STAT pathway are known mechanisms to induce PD-L1 expression in lymphoma cells...
May 8, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28482719/mef2c-dysregulated-pediatric-t-cell-acute-lymphoblastic-leukemia-is-associated-with-cdkn1b-deletions-and-a-poor-response-to-glucocorticoid-therapy
#5
Sara Colomer-Lahiguera, Markus Pisecker, Margit König, Karin Nebral, Winfried F Pickl, Maximilian O Kauer, Oskar A Haas, Reinhard Ullmann, Andishe Attarbaschi, Michael N Dworzak, Sabine Strehl
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease in which multiple genetic abnormalities cooperate in the malignant transformation of T-lymphoid progenitors. Although in pediatric T-ALL, CDKN1B deletions occur in about 12% of the cases and represent one of the most frequent copy number alterations, neither their association with other genetic alterations nor the clinical characteristics of these patients have been determined yet. In this study, we show that loss of CDKN1B increased the prevalence of cell cycle regulator defects in immature T-ALL, usually only ascribed to CDKN2A/B deletions, and that CDKN1B deletions frequently coincide with expression of MEF2C, considered as one of the driving oncogenes in immature early T-cell precursor (ETP) ALL...
May 9, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28464174/inverse-correlation-of-lymphoid-leukemia-incidence-and-anemia-prevalence-among-preschool-children
#6
Frank D Groves
OBJECTIVE: The relation between the prevalence of anemia and incidence of childhood acute lymphoblastic leukemia was explored using international cross-sectional data as well as US time-series data. METHODS: Lymphoid leukemia incidence rates for various countries from the International Agency for Research on Cancer were regressed on anemia prevalence rates from the World Health Organization in a cross-sectional analysis. Four decades of acute lymphoblastic leukemia incidence (from the Surveillance, Epidemiology, and End Results Program cancer registries) and anemia prevalence (from the National Health and Nutrition Examination Survey) also were examined in a time-series analysis...
May 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28456746/genetically-engineered-mesenchymal-stromal-cells-producing-il3-and-tpo-to-further-improve-human-scaffold-based-xenograft-models
#7
M Carretta, B de Boer, J Jaques, A Antonelli, S J Horton, H Yuan, J D de Bruijn, R W J Groen, E Vellenga, J J Schuringa
Recently, NOD-SCID IL2Rγ(-/-) (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or matrigel in order to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties [1-3]. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human IL3 and TPO...
April 26, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28449810/novel-t-5-11-q32-q13-4-with-numa1-pdgfrb-fusion-in-a-myeloid-neoplasm-with-eosinophilia-with-response-to-imatinib-mesylate
#8
Ying S Zou, Nicole L Hoppman, Zeba N Singh, Sameer Sawhney, Sandy D Kotiah, Maria R Baer
We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13...
April 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28444777/interphase-fish-for-bcr-abl1-rearrangement-on-neutrophils-a-decisive-tool-to-discriminate-a-lymphoid-blast-crisis-of-chronic-myeloid-leukemia-from-a-de-novo-bcr-abl1-positive-acute-lymphoblastic-leukemia
#9
Estelle Balducci, Marie Loosveld, Ilhem Rahal, John Boudjarane, Emilie Alazard, Chantal Missirian, Marina Lafage-Pochitaloff, Gérard Michel, Hélène Zattara
Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML...
April 25, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28433605/stability-of-patient-specific-features-of-altered-dna-replication-timing-in-xenografts-of-primary-human-acute-lymphoblastic-leukemia
#10
Takayo Sasaki, Juan Carlos Rivera-Mulia, Daniel Vera, Jared Zimmerman, Sunny Das, Michelle Padget, Naoto Nakamichi, Bill H Chang, Jeff Tyner, Brian J Druker, Andrew P Weng, Curt I Civin, Connie J Eaves, David M Gilbert
Genome-wide DNA replication timing (RT) profiles reflect the global 3D chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of the cellular epigenetic state. Thus normal differentiation involves reproducible changes in RT and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro...
April 19, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28424165/suppression-of-b-cell-development-genes-is-key-to-glucocorticoid-efficacy-in-treatment-of-acute-lymphoblastic-leukemia
#11
Karina Kruth, Mimi Fang, Dawne N Shelton, Ossama Abu-Halawa, Ryan Mahling, Hongxing Yang, Jonathan S Weissman, Mignon L Loh, Markus Müschen, Sarah K Tasian, Michael C Bassik, Martin Kampmann, Miles A Pufall
Glucocorticoids (GCs), including dexamethasone (dex), are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the glucocorticoid receptor (GR), a ligand-induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, which pathways affect their regulation, and how resistance arises are not well understood. Here we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation shRNA screen to identify GC-regulated "effector" genes that contribute to cell death as well as genes that affect the sensitivity of B-ALL cells to dex...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28401180/uncovering-a-new-cellular-origin-for-acute-myeloid-leukemia-with-lineage-plasticity
#12
REVIEW
Melinda Czeh, Frank Rosenbauer
Although acute myeloid leukaemia (AML) is assumed to be driven by transformed haematopoietic stem and progenitor cells, we have described recently a new pathway leading to AML from T-cell progenitors. Furthermore, we could identify a subgroup of human AML with gene expression profile suggesting T-lymphoid origin and potentially novel treatment.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28395813/prognostic-effect-of-complex-karyotype-monosomal-karyotype-and-chromosome-17%C3%A2-abnormalities-in-b-cell-acute-lymphoblastic-leukemia
#13
Priya Khoral, Eshetu G Atenafu, Kenneth J Craddock, Aaron Schimmer, Hong Chang
BACKGROUND: The effect of monosomal karyotype (MK), complex karyotype (CK), and chromosome 17 abnormalities (abnl 17) on prognosis in B-cell acute lymphoid leukemia (B-ALL) has not yet been established. PATIENTS AND METHODS: We conducted a retrospective analysis of prognostic factors on 237 adult patients with B-ALL treated at our institution. RESULTS: Older age (older than 60 years), higher white blood cell count (> 30), and abnl 17 were associated with shorter overall survival in univariate analysis, but multivariable analysis only identified older age as an independent poor prognostic actor...
April 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28394200/alteration-analysis-of-bone-marrow-mesenchymal-stromal-cells-from-de-novo-acute-myeloid-leukemia-patients-at-diagnosis
#14
Laura Desbourdes, Joaquim Javary, Thomas Charbonnier, Nicole Ishac, Jerome Bourgeais, Aurore Iltis, Jean-Claude Chomel, Ali Turhan, Fabien Guilloton, Karin Tarte, Marie-Veronique Demattei, Elfi Ducrocq, Florence Rouleux-Bonnin, Emmanuel Gyan, Olivier Hérault, Jorge Domenech
Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malignant clone or whether they are simply the effect of tumor expansion on the microenvironment. We extensively investigated the characteristics of MSCs isolated from the BM of patients with de novo AML at diagnosis (L-MSCs) in terms of phenotype (gene and protein expression, apoptosis and senescence levels, DNA double-strand break formation) and functions (proliferation and clonogenic potentials, normal and leukemic hematopoiesis-supporting activity)...
May 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28386358/dnmt3a-haploinsufficiency-cooperates-with-oncogenic-kras-to-promote-an-early-onset-t-cell-acute-lymphoblastic-leukemia
#15
Yuan-I Chang, Guangyao Kong, Erik A Ranheim, Po-Shu Tu, Yi-Shan Yu, Jing Zhang
Mutations in DNA methyltransferase 3A (DNMT3A) are prevalent in various myeloid and lymphoid malignancies. The most common DNMT3A R882 mutations inhibit methyltransferase activity of the remaining wild-type DNMT3A proteins at a heterozygous state due to their dominant-negative activity. Reports and COSMIC database analysis reveal significantly different frequencies of R882 mutations in myeloid versus T-cell malignancies, inspiring us to investigate whether downregulation of DNMT3A regulates malignancies of different lineages in a dose-dependent manner...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28375154/type-2-innate-lymphoid-cells-treat-and-prevent-acute-gastrointestinal-graft-versus-host-disease
#16
Danny W Bruce, Heather E Stefanski, Benjamin G Vincent, Trisha A Dant, Shannon Reisdorf, Hemamalini Bommiasamy, David A Serody, Justin E Wilson, Karen P McKinnon, Warren D Shlomchik, Paul M Armistead, Jenny P Y Ting, John T Woosley, Bruce R Blazar, Dietmar M W Zaiss, Andrew N J McKenzie, James M Coghill, Jonathan S Serody
Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#17
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
#18
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
#19
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
#20
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
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