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acute leukemia pathophysiology

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https://www.readbyqxmd.com/read/28592761/acute-lymphoblastic-leukemia-pathophysiology-and-current-therapy
#1
Kiyotoshi Imai
Acute lymphoblastic leukemia (ALL) is seen in both children and adults, but its incidence peaks between 2 and 5 years and also increases in the older population. Although most children can be cured, the prognosis of adults with ALL remains poor. Recent identification of novel genetic alterations and sequence mutations has contributed to the elucidation of the pathogenesis of ALL. The World Health Organization classification was revised in 2016. ALL was included within the subgroup of myeloid neoplasms and acute leukemia...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28591567/a-role-for-dystroglycan-in-the-pathophysiology-of-acute-leukemic-cells
#2
Lea Alonso-Rangel, Tizziani Benítez-Guerrero, Ivette Martínez-Vieyra, Bulmaro Cisneros, Adolfo Martínez-Tovar, Steve J Winder, Doris Cerecedo
AIMS: Previous reports have demonstrated that alterations or reduced expression of Dystroglycan (Dg) complex (αDg and βDg subunits) are related to progression and severity of neoplastic solid tissues. Therefore we determined the expression pattern and subcellular distribution of Dg complex in Acute Myeloid Leukemia (AML) primary blasts (M1, M2, and M3 phenotypes), as well as HL-60 and Kasumi-1 leukemia cell lines. Additionally, we evaluated the relative expression of the main enzymes controlling α-Dg glycosylation to ascertain the post-translational modifications in the leukemia cell phenotype...
June 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28566565/gata-transcription-factors-basic-principles-and-related-human-disorders
#3
Tohru Fujiwara
The development of mature blood cell from hematopoietic stem cells is regulated by transcription factors that coordinate the expression of lineage-specific genes. GATA transcription factors are zinc finger DNA-binding proteins that play crucial roles in various biological processes, including hematopoiesis. Among GATA family proteins, GATA-1, GATA-2, and GATA-3 are essential for hematopoiesis. GATA-1 functions to promote development of erythrocytes, megakaryocytes, eosinophils, and mast cells. Mutations in GATA-1 are associated with acute megakaryoblastic leukemia (AMKL), congenital erythroid hypoplasia (Diamond-Blackfan anemia; DBA), and X-linked anemia and/or thrombocytopenia...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28515935/methotrexate-encephalopathy-two-cases-in-adult-cancer-patients-who-recovered-with-pathophysiologically-based-therapy
#4
Shodeinde A Coker, David A Pastel, Melissa C Davis, Elizabeth M Bengtson, Camilo E Fadul, Lionel D Lewis
BACKGROUND/OBJECTIVES: Neurotoxicity is a serious and sometimes fatal adverse effect that can occur following methotrexate treatment. We describe two adult patients with hematological malignancies with methotrexate encephalopathy who recovered with dextromethorphan therapy. RESULTS: Case 1: A 24-year-old male with acute lymphoblastic leukemia developed the acute onset of bilateral facial weakness and slurred speech after his first treatment with high-dose intravenous methotrexate...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28503810/a-minor-role-of-asparaginase-in-predisposing-to-cerebral-venous-thromboses-in-adult-acute-lymphoblastic-leukemia-patients
#5
Saara Roininen, Outi Laine, Marjut Kauppila, Marko Vesanen, Maria Rämet, Marjatta Sinisalo, Esa Jantunen, Marjaana Säily, Riikka Räty, Erkki Elonen, Ulla Wartiovaara-Kautto
Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28379884/parental-alcohol-consumption-and-risk-of-leukemia-in-the-offspring-a-systematic-review-and-meta-analysis
#6
Maria A Karalexi, Nick Dessypris, Thomas P Thomopoulos, Evangelos Ntouvelis, Maria Kantzanou, Andreas-Antonios Diamantaras, Maria Moschovi, Margarita Baka, Emmanuel Hatzipantelis, Maria Kourti, Sophia Polychronopoulou, Eftichia Stiakaki, Ana-M Mora, Victor Wunsch-Filho, Claire Infante-Rivard, Dimitrios Loutradis, Eleni Th Petridou
Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies...
April 4, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28370201/a-phase-1-study-of-amg-900-an-orally-administered-pan-aurora-kinase-inhibitor-in-adult-patients-with-acute-myeloid-leukemia
#7
Hagop M Kantarjian, Michael W Schuster, Nitin Jain, Anjali Advani, Elias Jabbour, Erick Gamelin, Erik Rasmussen, Gloria Juan, Abraham Anderson, Vincent F Chow, Gregory Friberg, Florian D Vogl, Mikkael A Sekeres
Aurora kinases are involved in the pathophysiology of several cancers including acute myeloid leukemia (AML). In this phase 1 study, we investigated the safety and efficacy of AMG 900, an orally administered, highly potent, selective, small-molecule inhibitor of both Aurora kinase A and B, in patients with AML . Patients with pathologically documented AML who either declined standard treatments or had relapsed from or were refractory to previous therapies were enrolled. Two every-2-week dose-escalation schedules using a modified 3 + 3 + 3 design were evaluated AMG 900 given daily for 4 days with 10 days off (4/10 schedule), and AMG 900 given daily for 7 days with 7 days off (7/7 schedule)...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28320172/neuropathological-findings-from-an-autopsied-case-showing-posterior-reversible-encephalopathy-syndrome-like-neuroradiological-findings-associated-with-premedication-including-tacrolimus-for-autologous-peripheral-blood-stem-cell-transplantation
#8
Yuichi Hayashi, Akio Kimura, Hiroshi Nakamura, Maya Mimuro, Yasushi Iwasaki, Akira Hara, Mari Yoshida, Takashi Inuzuka
Posterior reversible encephalopathy syndrome (PRES) is diagnosed based on neuroradiological findings. Typically, PRES is reversible and presents with a good outcome; however, fatal outcomes have been reported. We report an autopsied case showing PRES-like neuroradiological findings associated with premedication including tacrolimus for autologous peripheral blood stem cell transplantation in a 28-year-old woman with a 2-year history of acute myeloid sarcoma/acute myeloid leukemia. Neurological examination revealed disturbed consciousness, muscle weakness in all extremities, and bilaterally diminished tendon reflexes...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28317081/pharmacogenetic-predictors-of-treatment-related-toxicity-among-children-with-acute-lymphoblastic-leukemia
#9
REVIEW
Rochelle R Maxwell, Peter D Cole
PURPOSE OF REVIEW: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). RECENT FINDINGS: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28239141/chronic-myeloid-leukemia-associated-hypercalcemia-a-case-report-and-literature-review
#10
REVIEW
David Toro-Tobón, Sarimar Agosto, Sara Ahmadi, Maureen Koops, Jan M Bruder
BACKGROUND Hypercalcemia associated with chronic myeloid leukemia (CML) is an ominous sign. Although rare, several cases have been reported and multiple pathophysiologic mechanisms have been independently proposed. We present a patient case and a literature review of the clinical presentation and mechanisms of CML-associated hypercalcemia. CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia...
February 27, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28154779/molecular-landscape-in-acute-myeloid-leukemia-where-do-we-stand-in-2016
#11
Karam Al-Issa, Aziz Nazha
Acute myeloid leukemia (AML) is a clonal disorder characterized by the accumulation of complex genomic alterations that define the disease pathophysiology and overall outcome. Recent advances in sequencing technologies have described the molecular landscape of AML and identified several somatic alterations that impact overall survival. Despite all these advancement, several challenges remain in translating this information into effective therapy. Herein we will review the molecular landscape of AML and discuss the impact of the most common somatic mutations on disease biology and outcome...
December 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28122581/acute-myeloid-leukemia-strategies-and-challenges-for-targeting-oncogenic-hedgehog-gli-signaling
#12
REVIEW
Fritz Aberger, Evelyn Hutterer, Christina Sternberg, Pedro J Del Burgo, Tanja N Hartmann
Treatment of acute myeloid leukemia (AML), an aggressive and heterogeneous hematological malignancy, remains a challenge. Despite advances in our understanding of the complex genetics and biology of AML pathophysiology, these findings have been translated to the clinic with only limited success, and poor outcomes persist for the majority of patients. Thus, novel treatment strategies are clearly needed for achieving deeper and prolonged remissions and for avoiding the development of resistance. Due to its profound role in (cancer) stem cell biology and differentiation, the Hedgehog (HH)/Glioma-associated Oncogene Homolog (GLI) signaling pathway may be an attractive novel therapeutic target in AML...
January 25, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28090484/mesenchymal-stromal-cells-in-myeloid-malignancies
#13
REVIEW
Thomas Schroeder, Stefanie Geyh, Ulrich Germing, Rainer Haas
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28060109/posterior-reversible-encephalopathy-syndrome-and-cerebral-sinus-thrombosis-in-a-case-of-pediatric-b-cell-all
#14
Ellen Fraint, Robin Miller, Andrew Walter
Posterior reversible encephalopathy syndrome (PRES) and cerebral sinus thrombosis are 2 known complications of acute lymphoblastic leukemia and its treatment. We describe a patient with acute lymphoblastic leukemia whose course was complicated by both of these conditions. This case is novel both for the fact that PRES developed before the initiation of therapy and that PRES was followed shortly by the development of cerebral sinus thrombosis. Our patient's story raises questions about our current understanding of the pathophysiology of PRES, and it suggests that PRES may actually be a predisposing risk factor for cerebral sinus thrombosis...
March 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28013226/disseminated-intravascular-coagulation
#15
REVIEW
Benjamin M Boral, Dennis J Williams, Leonard I Boral
OBJECTIVES: To provide a review of the definition, pathophysiology, differential diagnosis, and treatment of disseminated intravascular coagulation (DIC). METHODS: A case scenario and a review of the literature related to the pertinent facts concerning DIC are provided. RESULTS: DIC is a systemic pathophysiologic process and not a single disease entity, resulting from an overwhelming activation of coagulation that consumes platelets and coagulation factors and causes microvascular fibrin thrombi, which can result in multiorgan dysfunction syndrome from tissue ischemia...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28008177/mass-cytometry-analysis-reveals-hyperactive-nf-kappa-b-signaling-in-myelofibrosis-and-secondary-acute-myeloid-leukemia
#16
D A C Fisher, O Malkova, E K Engle, C A Miner, M C Fulbright, G K Behbehani, T B Collins, S Bandyopadhyay, A Zhou, G P Nolan, S T Oh
Myeloproliferative neoplasms (MPNs) feature a malignant clone containing the JAK2 V617F mutation, or another mutation causing dysregulated JAK2 kinase activity. The multiple disease phenotypes of MPNs, and their tendency to transform phenotypically, suggest pathophysiologic heterogeneities beyond a common phenomenon of JAK2 hyperactivation. JAK2 has the potential to activate multiple other signaling molecules, either directly through downstream effectors, or indirectly through induction of target gene expression...
February 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27913501/mutations-in-aml-prognostic-and-therapeutic-implications
#17
REVIEW
Courtney D DiNardo, Jorge E Cortes
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the proliferation and aberrant differentiation of immature clonal myeloid cells. The prognosis of AML is variable, based on clinical features such as patient age, performance status, and comorbidities, as well as leukemia-specific genetic features including cytogenetics and molecular classification. The modern application of next-generation sequencing technology has uncovered marked heterogeneity and genomic complexity within AML, based on the presence or absence of cooperating mutations within functional categories such as epigenetic regulators, cell signaling and proliferation pathways, and master hematopoietic transcription factors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27848185/pediatric-intestinal-beh%C3%A3-et-disease-complicated-by-myeloid-malignancies
#18
Kiichiro Kanamitsu, Akira Shimada, Ritsuo Nishiuchi, Tomonari Shigemura, Yozo Nakazawa, Kenichi Koike, Yuichi Kodama, Yuichi Shinkoda, Yoshifumi Kawano, Kozo Yasui, Koji Sasaki, Ryosuke Kajiwara, Hirokazu Tsukahara, Atsushi Manabe
Behçet disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown. We here retrospectively review pediatric-onset BD complicated by myeloid malignancies in Japan, having identified five such patients...
March 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27756750/the-emt-regulator-zeb2-is-a-novel-dependency-of-human-and-murine-acute-myeloid-leukemia
#19
Hubo Li, Brenton G Mar, Huadi Zhang, Rishi V Puram, Francisca Vazquez, Barbara A Weir, William C Hahn, Benjamin Ebert, David Pellman
Acute myeloid leukemia (AML) is a heterogeneous disease with complex molecular pathophysiology. To systematically characterize AML's genetic dependencies, we conducted genome-scale short hairpin RNA screens in 17 AML cell lines and analyzed dependencies relative to parallel screens in 199 cell lines of other cancer types. We identified 353 genes specifically required for AML cell proliferation. To validate the in vivo relevance of genetic dependencies observed in human cell lines, we performed a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/27752467/novel-therapeutic-options-in-acute-myeloid-leukemia
#20
REVIEW
Michael Medinger, Claudia Lengerke, Jakob Passweg
Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades...
2016: Leukemia Research Reports
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