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acute leukemia pathophysiology

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
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 PCR; however, a positive diagnosis was made after a brain biopsy. This and other published cases demonstrate that recipients of allogeneic stem cells can develop PML...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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
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...
February 14, 2018: Current Hematologic Malignancy Reports
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...
January 5, 2018: European Journal of Paediatric Neurology: EJPN
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
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 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 those patients was compared with that of controls. 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, female individuals: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria...
January 19, 2018: Haematologica
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
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...
January 15, 2018: Cellular Physiology and Biochemistry
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dorfel, 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 anti-leukemia reactivity...
January 10, 2018: Cancer Immunology Research
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 9, 2018: Small GTPases
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
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...
December 22, 2017: Current Opinion in Hematology
Edith Schneider, Anna Staffas, Linda Röhner, Erik D Malmberg, Arghavan Ashouri, Kathrin Krowiorz, Nicole Pochert, Christina Miller, Stella Yuan Wei, Laleh Arabanian, Christian Buske, Hartmut Döhner, Lars Bullinger, Linda Fogelstrand, Michael Heuser, Konstanze Döhner, Ping Xiang, Jens Ruschmann, Oleh I Petriv, Alireza Heravi-Moussavi, Carl L Hansen, Martin Hirst, R Keith Humphries, Arefeh Rouhi, Lars Palmqvist, Florian Kuchenbauer
Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected...
February 2018: Haematologica
Lawrence Van Helleputte, Mandy Kater, Dana P Cook, Caroline Eykens, Elisabeth Rossaert, Wanda Haeck, Tom Jaspers, Natasja Geens, Pieter Vanden Berghe, Conny Gysemans, Chantal Mathieu, Wim Robberecht, Philip Van Damme, Guido Cavaletti, Matthew Jarpe, Ludo Van Den Bosch
As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy...
March 2018: Neurobiology of Disease
Toshio Asayama, Hideto Tamura, Mariko Ishibashi, Yasuko Kuribayashi-Hamada, Asaka Onodera-Kondo, Namiko Okuyama, Akiko Yamada, Masumi Shimizu, Keiichi Moriya, Hidemi Takahashi, Koiti Inokuchi
T-cell immunoglobulin mucin-3 (Tim-3), an inhibitory immune checkpoint receptor, is highly expressed on acute myeloid leukemia cells and its ligand galectin-9 is reported to drive leukemic progression by binding with Tim-3. However, it remains unclear whether the Tim-3-galectin-9 pathway is associated with the pathophysiology of myelodysplastic syndromes (MDS). Thus, we investigated the expression and function of Tim-3 and the clinical impact of its ligand galectin-9 in MDS. Tim-3 expression levels on MDS blasts by CD45/side-scatter or CD34/CD45 gating were increased as MDS progressed to the advanced stage...
October 24, 2017: Oncotarget
José Arellano-Galindo, Alberto Parra Barrera, Elva Jiménez-Hernández, Sergio Zavala-Vega, Guillermina Campos-Valdéz, Juan Xicohtencatl-Cortes, Sara A Ochoa, Ariadnna Cruz-Córdova, María Del Pilar Crisóstomo-Vázquez, Juan Carlos Fernández-Macías, Juan Manuel Mejía-Aranguré
Acute leukemia is the most common pediatric cancer, representing one-third of all cancers that occurs in under 15 year olds, with a varied incidence worldwide. Although a number of advances have increased the knowledge of leukemia pathophysiology, its etiology remains less well understood. The role of infectious agents, such as viruses, bacteria, or parasites, in the pathogenesis of leukemia has been discussed. To date, several cellular mechanisms involving infectious agents have been proposed to cause leukemia following infections...
May 2017: Archives of Medical Research
Lisa M Blackburn, Shelly Brown, Aimee Munyon, Michelle Orovets
BACKGROUND: Hyperleukocytosis, a peripheral white blood cell count greater than 100,000/mm3,is most commonly seen in patients with newly diagnosed or relapsed acute lymphoblastic leukemia and acute myeloid leukemia. Leukostasis is a reduction in blood flow related to hyperviscosity. Hyperleukocytosis, causing leukostasis, is an oncologic emergency and requires an exacting assessment and rapid response with appropriate intervention to prevent morbidity and mortality in the first week after diagnosis...
December 1, 2017: Clinical Journal of Oncology Nursing
Vered Shkalim-Zemer, Itzhak Levi, Salvador Fischer, Hannah Tamary, Joanne Yakobovich, Gali Avrahami, Gil Gilad, Sara Elitzur, Isaac Yaniv, Ronit Elhasid, Michal Manistersky, Itamar Shalit
BACKGROUND: Chronic disseminated candidiasis (CDC) is a severe invasive fungal infection principally observed during neutrophil recovery in patients with acute leukemia treated with intensive chemotherapy. Its pathophysiology remains unclear. We describe the management of six children with symptomatic CDC who did not respond to antifungal therapy. METHODS: The databases of the hematology-oncology departments of two tertiary pediatric medical centers were searched for all patients diagnosed with CDC from 2003 to 2015 who responded to corticosteroids after failing antifungal therapy...
November 14, 2017: Pediatric Infectious Disease Journal
Hakan Ozdogan, Bala Gur Dedeoglu, Yasemin Oztemur Islakoglu, Alp Aydos, Sevil Kose, Arzu Atalay, Zeynep Arzu Yegin, Ferit Avcu, Duygu Uckan Cetinkaya, Osman Ilhan
Multipotent mesenchymal stem cells (MSC) are key components of the bone marrow (BM) microenvironment. The contribution of this microenvironment to the pathophysiology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is not well defined. A recent study in mice demonstrated that DICER1 gene deletion in osteoprogenitor cells from the BM microenvironment suppressed osteogenic differentiation and induced MDS and AML-like haematological findings. The present study evaluated the expression profiles of microRNAs (miRNAs) and DICER1 gene in BM-derived MSC of patients with AML (n=12), MDS (n=10) and healthy controls (HC) (n=8)...
December 2017: Leukemia Research
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