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acute lymphoblastic leukemia -L3 type

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https://www.readbyqxmd.com/read/28225303/initial-diagnostic-workup-of-acute-leukemia-guideline-from-the-college-of-american-pathologists-and-the-american-society-of-hematology
#1
Daniel A Arber, Michael J Borowitz, Melissa Cessna, Joan Etzell, Kathryn Foucar, Robert P Hasserjian, J Douglas Rizzo, Karl Theil, Sa A Wang, Anthony T Smith, R Bryan Rumble, Nicole E Thomas, James W Vardiman
CONTEXT: -A complete diagnosis of acute leukemia requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and often, molecular genetic testing. Although many aspects of the workup for acute leukemia are well accepted, few guidelines have addressed the different aspects of the diagnostic evaluation of samples from patients suspected to have acute leukemia. OBJECTIVE: -To develop a guideline for treating physicians and pathologists involved in the diagnostic and prognostic evaluation of new acute leukemia samples, including acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage...
February 22, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28196983/genomic-profiling-of-acute-lymphoblastic-leukemia-in-ataxia-telangiectasia-patients-reveals-tight-link-between-atm-mutations-and-chromothripsis
#2
M Ratnaparkhe, M Hlevnjak, T Kolb, A Jauch, K K Maass, F Devens, A Rode, V Hovestadt, A Korshunov, A Pastorczak, W Mlynarski, S Sungalee, J Korbel, J Hoell, U Fischer, T Milde, C Kramm, M Nathrath, K Chrzanowska, E Tausch, M Takagi, T Taga, S Constantini, J Loeffen, J Meijerink, S Zielen, G Gohring, B Schlegelberger, E Maass, R Siebert, J Kunz, A E Kulozik, B Worst, D T Jones, S M Pfister, M Zapatka, P Lichter, A Ernst
Recent developments in sequencing technologies led to the discovery of a novel form of genomic instability, termed chromothripsis. This catastrophic genomic event, involved in tumorigenesis, is characterized by tens to hundreds of simultaneously acquired locally clustered rearrangements on one chromosome. We hypothesized that leukemias developing in individuals with Ataxia Telangiectasia, who are born with two mutated copies of the ATM gene, an essential guardian of genome stability, would show a higher prevalence of chromothripsis due to the associated defect in DNA double-strand break repair...
February 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28195091/coagulation-profile-during-induction-chemotherapy-in-childhood-acute-lymphoblastic-leukemia
#3
Shivali Sehgal, Sunita Sharma, Jagdish Chandra, Anita Nangia
CONTEXT: Thromboembolism in children with acute lymphoblastic leukemia (ALL) is most commonly reported after the initiation of antileukemic therapy, indicating a possible interaction of disease and therapy. AIMS: To study the effect of induction chemotherapy on coagulation parameters in pediatric ALL patients. SETTINGS AND DESIGN: Thirty-seven newly diagnosed patients of ALL up to 18 years of age were evaluated along with 30 age- and sex-matched controls...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28193268/adipokines-insulin-resistance-and-adiposity-as-a-predictors-of-metabolic-syndrome-in-child-survivors-of-lymphoma-and-acute-lymphoblastic-leukemia-of-a-developing-country
#4
Lourdes Barbosa-Cortés, Mardia López-Alarcón, Juan Manuel Mejía-Aranguré, Miguel Klünder-Klünder, María Del Carmen Rodríguez-Zepeda, Hugo Rivera-Márquez, Alan de la Vega-Martínez, Jorge Martin-Trejo, Juan Shum-Luis, Karina Solis-Labastida, Enrique López-Aguilar, Guadalupe Matute-González, Roberto Bernaldez-Rios
BACKGROUND: There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. METHODS: Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study...
February 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28179279/role-of-runx1-in-hematological-malignancies
#5
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/28179212/association-between-n363s-and-bcli-polymorphisms-of-the-glucocorticoid-receptor-gene-nr3c1-and-glucocorticoid-side-effects-during-childhood-acute-lymphoblastic-leukemia-treatment
#6
Meriç Kaymak Cihan, Halil Gürhan Karabulut, Nüket Yürür Kutlay, Hatice Ilgın Ruhi, Ajlan Tükün, Lale Olcay
OBJECTIVE: Glucocorticoids (GCs) are the key drugs for the treatment of pediatric acute lymphoblastic leukemia (ALL). Herein, investigation of the relationship between the N363S and BclI polymorphisms of the GC receptor gene (NR3C1) and the side effects of GCs during pediatric ALL therapy was aimed. MATERIALS AND METHODS: N363S and BclI polymorphisms were analyzed in 49 patients with ALL treated between 2000 and 2012. Control group consisted 46 patients with benign disorders...
February 9, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28165340/targeting-the-adenosine-2a-receptor-enhances-chimeric-antigen-receptor-t-cell-efficacy
#7
Paul A Beavis, Melissa A Henderson, Lauren Giuffrida, Jane K Mills, Kevin Sek, Ryan S Cross, Alexander J Davenport, Liza B John, Sherly Mardiana, Clare Y Slaney, Ricky W Johnstone, Joseph A Trapani, John Stagg, Sherene Loi, Lev Kats, David Gyorki, Michael H Kershaw, Phillip K Darcy
Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs)...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28159681/the-dual-specificity-pi3k-mtor-inhibitor-pki-587-displays-efficacy-against-t-cell-acute-lymphoblastic-leukemia-t-all
#8
Mohiuddin Gazi, Sausan A Moharram, Alissa Marhäll, Julhash U Kazi
Although significant improvements have been made in the treatment of acute lymphoblastic leukemia (ALL), there is a substantial subset of high-risk T-cell ALL (T-ALL) patients with relatively poor prognosis. Like in other leukemia types, alterations of the PI3K/mTOR pathway are predominant in ALL which is also responsible for treatment failure and relapse. In this study, we show that relapsed T-ALL patients display an enrichment of the PI3K/mTOR pathway. Using a panel of inhibitors targeting multiple components of the PI3K/mTOR pathway, we observed that the dual-specific PI3K/mTOR inhibitor PKI-587 was the most selective inhibitor for T-ALL cells dependent on the PI3K/mTOR pathway...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28157215/identification-of-a-genetically-defined-ultra-high-risk-group-in-relapsed-pediatric-t-lymphoblastic-leukemia
#9
P Richter-Pechańska, J B Kunz, J Hof, M Zimmermann, T Rausch, O R Bandapalli, E Orlova, G Scapinello, J C Sagi, M Stanulla, M Schrappe, G Cario, R Kirschner-Schwabe, C Eckert, V Benes, J O Korbel, M U Muckenthaler, A E Kulozik
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher's exact test), inactivation of TP53 (P=0.0007, Fisher's exact test) and duplication of chr17:q11.2-24.3 (P=0...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28152872/racial-and-ethnic-disparities-in-the-survival-of-adolescents-and-young-adults-aya-with-acute-myeloid-leukemia-aml
#10
Adam C Bartley, Ronald S Go
: 297 Background: Unlike acute lymphoblastic leukemia, no studies have examined the effect of race on survival among AML in AYA using national data. METHODS: We studied patients in the US National Cancer Data Base aged 15-39 diagnosed with AML from 2001-2011 (excluding acute promyelocytic leukemia). AMLs harboring inv(16) or t(8;21) were defined as good-risk. We examined overall survival (OS) according to race/ethnicity and survival trends over three time-periods: 2001-2004, 2005-2008, and 2009-2011...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28150907/venous-thromboembolism-following-l-asparaginase-treatment-for-lymphoid-malignancies-in-korea
#11
J H Lee, J Lee, H-Y Yhim, D Oh, S-M Bang
BACKGROUND: L-asparaginase (L-asp) associated venous thromboembolism (VTE) is a serious adverse complication associated with acute lymphoblastic leukemia (ALL) and lymphoma treatment. The incidence rate of L-asp related VTE in Asian cancer patients is not well known. METHODS: We performed a population-based study between 2009 and 2013 using claim databases including both diagnostic and medication codes, such as anti-cancer treatment with L-asp, and VTE diagnoses from the starting date until 3 months after cessation of L-asp...
February 2, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28121440/dioncophyllines-c2-d2-and-f-and-related-naphthylisoquinoline-alkaloids-from-the-congolese-liana-ancistrocladus-ileboensis-with-potent-activities-against-plasmodium-falciparum-and-against-multiple-myeloma-and-leukemia-cell-lines
#12
Jun Li, Raina Seupel, Doris Feineis, Virima Mudogo, Marcel Kaiser, Reto Brun, Daniela Brünnert, Manik Chatterjee, Ean-Jeong Seo, Thomas Efferth, Gerhard Bringmann
Dioncophylline F (1), the first 5,8'-coupled dioncophyllaceous alkaloid (i.e., lacking an oxygen function at C-6 and possessing an R-configuration at C-3), was isolated from the recently described Congolese liana Ancistrocladus ileboensis. Two further, likewise Dioncophyllaceae-type, alkaloids, the dioncophyllines C2 (2) and D2 (3), were identified, along with the Ancistrocladaceae-type compound ancistrocladisine B (4), which is oxygenated at C-6 and S-configured at C-3. The structures of the new compounds were determined by spectroscopic, chemical, and chiroptical methods...
January 25, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28119366/bioluminescence-imaging-enhances-analysis-of-drug-responses-in-a-patient-derived-xenograft-model-of-pediatric-all
#13
Luke Jones, Jennifer Richmond, Kathryn Evans, Hernan Carol, Duohui Jing, Raushan T Kurmasheva, Catherine A Billups, Peter J Houghton, Malcolm A Smith, Richard B Lock
PURPOSE: Robust preclinical models of pediatric acute lymphoblastic leukemia (ALL) are essential in prioritizing promising therapies for clinical assessment in high-risk patients. Patient-derived xenograft (PDX) models of ALL provide a clinically relevant platform for assessing novel drugs, with efficacy generally assessed by enumerating circulating human lymphoblasts in mouse peripheral blood (PB) as an indicator of disease burden. While allowing indirect measurement of disease burden in real-time, this technique cannot assess treatment effects on internal reservoirs of disease...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28099272/mixed-phenotype-acute-leukemia-current-challenges-in-diagnosis-and-therapy
#14
Ofir Wolach, Richard M Stone
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors...
March 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28090485/mixed-phenotype-acute-leukemia-suboptimal-treatment-when-the-2008-2016-who-classification-is-used
#15
Alan Pomerantz, Sergio Rodriguez-Rodriguez, Roberta Demichelis-Gomez, Georgina Barrera-Lumbreras, Olga Barrales-Benitez, Xavier Lopez-Karpovitch, Alvaro Aguayo-Gonzalez
BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#16
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28063690/influence-of-musculoskeletal-manifestations-as-the-only-presenting-symptom-in-b-cell-acute-lymphoblastic-leukemia
#17
Seungcheol Kang, Ho Joon Im, Kunhyung Bae, Soo-Sung Park
OBJECTIVE: To evaluate the clinical and prognostic impact of musculoskeletal manifestations as the only initial presenting symptom in childhood acute lymphoblastic leukemia (ALL). STUDY DESIGN: We retrospectively reviewed 158 children with precursor B-cell type ALL who were followed up for >2 years. The patients were assigned to the groups musculoskeletal manifestations (n = 24) or nonmusculoskeletal manifestations (n = 134) based on initial presenting symptom...
January 4, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28050230/givinostat-a-type-ii-histone-deacetylase-inhibitor-induces-potent-caspase-dependent-apoptosis-in-human-lymphoblastic-leukemia
#18
Ying Li, Kevin Zhao, Chenjiao Yao, Samir Kahwash, Yan Tang, Guojiuan Zhang, Kara Patterson, Qi-En Wang, Weiqiang Zhao
Unlike chronic myeloid leukemia, patients with acute lymphoblastic leukemia (ALL) with Philadelphia chromosome (Ph+) do not respond well to Imatinib or tyrosine kinase inhibitors (TKI). In addition, TKI might induce resistant mutations in kinase domain (KD) of ABL in patients with relapsed diseases. Of the histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic acid (SAHA) has shown to induce potent cytotoxicity on acute myeloid leukemia cell lines but Givinostat effect on acute lymphoblastic leukemia (ALL) has not been reported...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28033648/characterisation-of-the-genomic-landscape-of-crlf2-rearranged-acute-lymphoblastic-leukemia
#19
Lisa J Russell, Lisa Jones, Amir Enshaei, Stefano Tonin, Sarra L Ryan, Jeyanthy Eswaran, Sirintra Nakjang, Elli Papaemmanuil, Jose M C Tubio, Adele K Fielding, Ajay Vora, Peter J Campbell, Anthony V Moorman, Christine J Harrison
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%)...
December 29, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28028966/glycogen-synthase-kinase-3%C3%AE-gsk-3%C3%AE-and-nuclear-factor-kappa-b-nfkb-in-childhood-acute-lymphoblastic-leukemia
#20
Cristian Fabian Layton Tovar, Hugo Mendieta Zerón, Maria Del Socorro Camarillo Romero, Yanko V Fabila Sánchez, Isidoro Tejocote Romero
BACKGROUND: Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in early childhood. In children with acute lymphoblastic leukemia (ALL), the activity of glycogen synthase kinase (GSK-3β) has been associated with changes in the transcriptional activity and expression of nuclear factor kappa beta (NFKB) in the mononuclear cells of bone marrow. OBJECTIVES: The aim of the study was to determine the possible role of glycogen synthase kinase 3beta (GSK-3β) and nuclear factor kappa beta (NFKB) as prognostic variables in pediatric patients with ALL...
November 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
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