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acute leukemia pathophysiology

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https://www.readbyqxmd.com/read/29766829/acute-myeloid-leukemia-diagnosis-and-management-based-on-current-molecular-genetics-approach
#1
E Suguna, R Farhana, E Kanimozhi, P SaiKumar, G Kumaramanickavel, Chitralekha Sai Kumar
Background &Objective: Acute myeloid leukemia (AML) is characterized by accumulation of ?20% myeloid premature blast cells in the bone marrow and most often found in the peripheral blood. AML is generally classified based on two groups, namely, French-American-British (FAB) and World Health Organization (WHO) systems. For better clinical management, cytogenetic findings in AML are necessary and in patients with normal karyotypes, molecular analysis becomes critical. Mutations of certain genes like Nucleophosmin 1gene (NPM1), Fms-related Tyrosine Kinase 3 (FLT3), CCAAT/Enhancer Binding Protein Alpha (CEBPA), Runt-related transcription factor 1(RUNX1), and Mixed Lineage Leukemia (MLL) play a crucial role in the risk management and clinical stratification of AML patients...
May 15, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29762237/growth-plate-suppression-in-an-adolescent-patient-with-acute-lymphoblastic-leukemia-after-treatment
#2
Ekaterina Tiktinsky, Daniel Levin, Sophia Lantsberg, Joseph Kapelushnik
Osteotoxic effect is a common adverse effect of chemotherapy for childhood acute lymphoblastic leukemia. The pathophysiology of impaired bone growth is multifactorial and can affect both osteoblast and osteoclast function. Significant contribution in affecting skeletal metabolism belongs to high-dose corticosteroid treatment. We present the case of a 12-year-old adolescent girl who was treated for high-risk pro-B acute lymphoblastic leukemia. The Tc-MDP bone scan, as a sensitive indicator of osteoblastic activity, shows that growth plate inhibition after intensive treatment may be temporary and reversible...
May 14, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29742289/the-genetic-and-molecular-pathogenesis-of-myelodysplastic-syndromes
#3
REVIEW
Rory M Shallis, Rami Ahmad, Amer M Zeidan
Myelodysplastic syndromes (MDS) comprise a diverse group of clonal and malignant myeloid disorders characterized by ineffective hematopoiesis, resultant peripheral cytopenias, and a meaningful increased risk of progression to acute myeloid leukemia. A wide array of recurring genetic mutations involved in RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements have been identified as important substrates for the development of MDS...
May 9, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29703489/mechanisms-and-management-of-coagulopathy-in-acute-promyelocytic-leukemia
#4
Sachin David, Vikram Mathews
Acute promyelocytic leukemia (APL) is a subtype of leukemia which is associated with unique and distinctive coagulopathy. In the absence of treatment it is rapidly fatal and even after initiation of therapy the major cause of early mortality is related to hemorrhagic complications. The coagulopathy can be exacerbated with the start of treatment. In the absence of early hemorrhage related deaths the probability of cure exceeds 90% in low and intermediate risk patients and 80% even in high risk patients, highlighting the importance of understanding the pathophysiology of this complication and instituting prompt and appropriate management strategies...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29669823/recurrent-patterns-of-protein-expression-signatures-in-pediatric-acute-lymphoblastic-leukemia-recognition-and-therapeutic-guidance
#5
Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Andrew Ligeralde, Suk-Young Yoo, Eveline Sjm De Bont, Amina A Qutub, Terzah M Horton, Steven M Kornblau
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and the second leading cause of pediatric cancer death in developed countries. While the cure rate for newly-diagnosed ALL is excellent, the genetic heterogeneity and chemoresistance of leukemia cells at relapse makes individualized curative treatment plans difficult. We hypothesize that genetic events would coalesce into a finite number of protein signatures that could guide the design of individualized therapy. Custom Reverse Phase Protein Arrays were produced from pediatric ALL (n=73) and normal CD34+ (n=10) samples with 194 validated antibodies...
April 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29667769/targeting-the-phosphatidylinositol-3-kinase-akt-mechanistic-target-of-rapamycin-signaling-pathway-in-b-lineage-acute-lymphoblastic-leukemia-an-update
#6
REVIEW
Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Marco Vitale, James A McCubrey, Silvano Capitani, Luca M Neri
Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease...
April 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29665908/-significance-of-retinol-binding-protein-expression-in-patients-with-acute-myeloid-leukemia
#7
Wei Tang, Xian Li, Zhen-Zhuo Ma, Chun-Ying Li
OBJECTIVE: To investigate the expression of retinol-binding protein (RBP) in patients with acute myeloid leukemia (AML) and its related factors. METHODS: The clinical data of 123 patients with AML from October 2012 to February 2016 and 100 healthy controls were collected and the correlation of RBP expression level with sex, French-American-British (FAB) subtypes, molecular mutations, peripheral white blood cells and long-term outcomes was analyzed. RESULTS: Compared with AML patients, the RBP expression level was significantly higher in healthy controls (61...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29527516/epigenetic-regulators-in-the-development-maintenance-and-therapeutic-targeting-of-acute-myeloid-leukemia
#8
REVIEW
Younguk Sun, Bo-Rui Chen, Aniruddha Deshpande
The importance of epigenetic dysregulation to acute myeloid leukemia (AML) pathophysiology has become increasingly apparent in recent years. Epigenetic regulators, including readers, writers, and erasers, are recurrently dysregulated by way of chromosomal translocations, somatic mutations, or genomic amplification in AML and many of these alterations are directly implicated in AML pathogenesis. Mutations in epigenetic regulators are often discovered in founder clones and persist after therapy, indicating that they may contribute to a premalignant state poised for the acquisition of cooperating mutations and frank malignancy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29512846/progressive-multifocal-leukoencephalopathy-after-allogeneic-stem-cell-transplantation-case-report-and-review-of-the-literature
#9
Cai Yuan, Candace Deberardinis, Rushang Patel, Seema M Shroff, Steven A Messina, Steven Goldstein, Shahram Mori
Progressive multifocal leukoencephalopathy (PML) is a rare, yet typically fatal complication of allogeneic stem cell transplantation. It is caused by reactivation of the John Cunningham (JC) virus in an immunocompromised host. This report describes an unfortunate case of PML in a recipient of an allogeneic stem cell transplant for acute myelogenous leukemia. The JC virus was undetectable in the patient's cerebrospinal fluid by polymerase chain reaction (PCR); however, a positive diagnosis was made after a brain biopsy...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29464086/snp-array-lesions-in-core-binding-factor-acute-myeloid-leukemia
#10
Nicolas Duployez, Elise Boudry-Labis, Christophe Roumier, Nicolas Boissel, Arnaud Petit, Sandrine Geffroy, Nathalie Helevaut, Karine Celli-Lebras, Christine Terré, Odile Fenneteau, Wendy Cuccuini, Isabelle Luquet, Hélène Lapillonne, Catherine Lacombe, Pascale Cornillet, Norbert Ifrah, Hervé Dombret, Guy Leverger, Eric Jourdan, Claude Preudhomme
Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29442287/recent-developments-in-adolescent-and-young-adult-aya-acute-lymphoblastic-leukemia
#11
REVIEW
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
April 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29396168/small-fiber-neuropathy-and-pain-sensitization-in-survivors-of-pediatric-acute-lymphoblastic-leukemia
#12
S Lieber, M Blankenburg, K Apel, G Hirschfeld, P Hernáiz Driever, T Reindl
BACKGROUND: Chemotherapy-induced Peripheral Neuropathy (CIPN) of large-fibers affects up to 20% of survivors of pediatric acute lymphoblastic leukemia (ALL). We aimed to describe small-fiber toxicity and pain sensitization in this group. METHODS: In a cross-sectional, bicentric study we assessed 46 survivors of pediatric ALL (Mean age: 5.7 ± 3.5 years at diagnosis, median 2.5 years after therapy; males: 28). INCLUSION CRITERIA: ≥6 years of age, ≥3 months after last administration of Vincristine, and cumulative dose of Vincristine 12 mg/m2 ...
May 2018: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29394974/proteomic-profile-of-lymphoid-leukemia
#13
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
https://www.readbyqxmd.com/read/29351982/prevalence-and-characteristics-of-metabolic-syndrome-in-adults-from-the-french-childhood-leukemia-survivors-cohort-a-comparison-with-controls-from-the-french-population
#14
Claire Oudin, Julie Berbis, Yves Bertrand, Camille Vercasson, Frédérique Thomas, Pascal Chastagner, Stéphane Ducassou, Justyna Kanold, Marie-Dominique Tabone, Catherine Paillard, Marilyne Poirée, Dominique Plantaz, Jean-Hugues Dalle, Virginie Gandemer, Sandrine Thouvenin, Nicolas Sirvent, Paul Saultier, Sophie Béliard, Guy Leverger, André Baruchel, Pascal Auquier, Bruno Pannier, Gérard Michel
The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria...
April 2018: Haematologica
https://www.readbyqxmd.com/read/29340257/symmetrical-drug-related-intertriginous-and-flexural-exanthema-induced-by-doxycycline
#15
David G Li, Cristina Thomas, Gil S Weintraub, Arash Mostaghimi
Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by erythema over the buttocks, thighs, groin, and flexural regions most commonly associated with the use of beta-lactam antibiotics. Although the exact pathophysiology of this disease remains unknown, it is theorized to be the result of a delayed hypersensitivity response presenting as a cutaneous eruption days to weeks after exposure to the drug. The treatment involves discontinuation of the suspected medication, symptomatic control of pruritus, and topical steroid therapy...
November 10, 2017: Curēus
https://www.readbyqxmd.com/read/29339628/downregulation-of-long-non-coding-rna-kcnq1ot1-an-important-mechanism-of-arsenic-trioxide-induced-long-qt-syndrome
#16
Yanan Jiang, Weijie Du, Qun Chu, Ying Qin, Gulnara Tuguzbaeva, Hui Wang, Anqi Li, Guiyang Li, Yanyao Li, Lu Chai, Er Yue, Xi Sun, Zhiguo Wang, Valentin Pavlov, Baofeng Yang, Yunlong Bai
BACKGROUND/AIMS: Arsenic trioxide (ATO) is a known anti-acute promyelocytic leukemia (APL) reagent, whose clinical applications are limited by its serious cardiac toxicity and fatal adverse effects, such as sudden cardiac death resulting from long QT syndrome (LQTS). The mechanisms of cardiac arrhythmia due to ATO exposure still need to be elucidated. Long non-coding RNAs (lncRNAs) are emerging as major regulators of various pathophysiological processes. This study aimed to explore the involvement of lncRNAs in ATO-induced LQTS in vivo and in vitro...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29321210/the-immune-checkpoint-modulator-ox40-and-its-ligand-ox40l-in-nk-cell-immunosurveillance-and-acute-myeloid-leukemia
#17
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dörfel, Pascal Schneider, Gundram Jung, Helmut Rainer Salih
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here, we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and antileukemia reactivity...
February 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancer-a
#18
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 24, 2018: Small GTPases
https://www.readbyqxmd.com/read/29296741/osteonecrosis-in-children-and-adolescents-with-acute-lymphoblastic-leukemia-a-therapeutic-challenge
#19
REVIEW
Michaela Kuhlen, Marina Kunstreich, Kathinka Krull, Roland Meisel, Arndt Borkhardt
Osteonecrosis (ON) represents one of the most common and debilitating sequelae of antileukemic treatment in children and adolescents with acute lymphoblastic leukemia (ALL). Systematic screening strategies can focus on early detection and intervention to prevent ON from progressing to stages associated with pain and functional impairment. These strategies hold promise for reducing ON-associated morbidity without the risk of impairing leukemia control. Herein, we critically reviewed clinical data on pharmacological, nonpharmacological/nonsurgical, and surgical (including cellular) treatment options for ON, which are covered in the literature and/or are conceivable based on the supposed underlying ON pathophysiology...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29278534/cohesin-mutations-in-myeloid-malignancies-made-simple
#20
Aaron D Viny, Ross L Levine
PURPOSE OF REVIEW: Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer RECENT FINDINGS: The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division...
March 2018: Current Opinion in Hematology
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