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acute leukemia pathophysiology

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https://www.readbyqxmd.com/read/29149122/leukostasis-management-to-prevent-crisis-in-acute-leukemia%C3%A2
#1
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
https://www.readbyqxmd.com/read/29140934/response-of-symptomatic-persistent-chronic-disseminated-candidiasis-to-corticosteroid-therapy-in-immunosuppressed-pediatric-patients-case-study-and-review-of-the-literature
#2
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
https://www.readbyqxmd.com/read/29102598/dicer1-gene-and-mirna-dysregulation-in-mesenchymal-stem-cells-of-patients-with-myelodysplastic-syndrome-and-acute-myeloblastic-leukemia
#3
Hakan Ozdogan, Bala Gur Dedeoglu, Yasemin Oztemur Islakoglu, Alp Aydos, Sevil Kose, Arzu Atalay, Zeynep Arzu Yegin, Ferit Avcu, Duygu Ocean 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)...
October 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29090344/the-role-of-mutant-idh1-and-idh2-inhibitors-in-the-treatment-of-acute-myeloid-leukemia
#4
REVIEW
Samah Nassereddine, Coen J Lap, Faysal Haroun, Imad Tabbara
For decades, researchers have looked into the pathophysiology of acute myeloid leukemia (AML). With the advances in molecular techniques, the two-hit hypothesis was replaced by a multi-hit model, which also emphasizes the importance of aberrant epigenetic regulation in the pathogenesis of AML. IDH1 and IDH2 are two isoforms of isocitrate dehydrogenase that perform crucial roles in cellular metabolism. Somatic mutations in either of these two genes impart a neomorphic enzymatic activity upon the encoded enzymes resulting in the ability to convert α-ketoglutarate (αKG) into the oncometabolite R2-hydroxyglutarate (R2-HG), which can competitively inhibit multiple αKG-dependent dioxygenases...
October 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29034206/leukemia-initiating-cells-in-t-cell-acute-lymphoblastic-leukemia
#5
REVIEW
Shi Hao Tan, Fatima Carla Bertulfo, Takaomi Sanda
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29024628/biologico-clinical-significance-of-dnmt3a-variants-expression-in-acute-myeloid-leukemia
#6
Na Lin, Wei Fu, Chen Zhao, Bixin Li, Xiaojing Yan, Yan Li
DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays important roles in the pathogenesis of acute myeloid leukemia. However, the expression status of DNMT3A variants in acute myeloid leukemia remains obscure. This study aimed to assess the expression levels of alternative splicing of DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A variants gene expression were assessed, measuring their effects on cell proliferation. In addition, the expression of DNMT3A variants were evaluated in acute myeloid leukemia patients...
October 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28992762/mutations-in-tet2-and-dnmt3a-genes-are-associated-with-changes-in-global-and-gene-specific-methylation-in-acute-myeloid-leukemia
#7
Alberto Ponciano-Gómez, Adolfo Martínez-Tovar, Jorge Vela-Ojeda, Irma Olarte-Carrillo, Federico Centeno-Cruz, Efraín Garrido
Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28989535/investigating-the-microrna-mrna-regulatory-network-in-acute-myeloid-leukemia
#8
Haiguo Zhang, Chengfang Zhang, Rui Feng, Haixia Zhang, Min Gao, Ling Ye
Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28965757/erythroleukemia-historical-perspectives-and-recent-advances-in-diagnosis-and-management
#9
REVIEW
Prajwal Boddu, Christopher B Benton, Wei Wang, Gautam Borthakur, Joseph D Khoury, Naveen Pemmaraju
Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblastic proliferation. After a century of its descriptive history, many diagnostic, prognostic, and therapeutic implications relating to this unique leukemia subset remain uncertain. The rarity of the disease and the simultaneous involvement of its associated myeloid compartment have complicated in vitro studies of human erythroleukemia cell lines. Although murine and cell line erythroleukemia models have provided valuable insights into pathophysiology, translation of these concepts into treatment are not forthcoming...
September 18, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28965123/identification-of-mirna-mrna-network-associated-with-acute-myeloid-leukemia-survival
#10
Chunmei Zhang, Guanchen Bai, Weijie Zhu, Dongfang Bai, Gaofeng Bi
BACKGROUND Acute myeloid leukemia (AML) is a common hematologic malignancy of adults. The pathophysiological mechanism of AML is not well understood. The purpose of this study was to examine the crucial miRNAs and mRNAs associated with AML survival. MATERIAL AND METHODS The full clinical dataset of miRNA and mRNA expression profiling of AML patients was downloaded from The Cancer Genome Atlas database. Univariate Cox regression analysis was performed to obtain those miRNAs and mRNAs associated with AML survival...
October 1, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28841588/thrombosis-in-adult-patients-with-acute-leukemia
#11
Maria Ilaria Del Principe, Domenico Del Principe, Adriano Venditti
PURPOSE OF REVIEW: Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. RECENT FINDINGS: In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#12
REVIEW
Soumyasri Das Gupta, Zohar Sachs
Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs...
November 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28758276/brief-report-human-acute-myeloid-leukemia-reprograming-to-pluripotency-is-a-rare-event-and-selects-for-patient-hematopoietic-cells-devoid-of-leukemic-mutations
#13
Jong-Hee Lee, Kyle R Salci, Jennifer C Reid, Luca Orlando, Borko Tanasijevic, Zoya Shapovalova, Mickie Bhatia
Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades...
July 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28731917/the-impact-of-iron-overload-in-acute-leukemia-chronic-inflammation-but-not-the-presence-of-nontransferrin-bound-iron-is-a-determinant-of-oxidative-stress
#14
Lale Olcay, Mustafa Serteser, Murat Kolay, Havva F Balci, Ülkü M Yildirim, Sibel A Tekgündüz, Tuncay Hazirolan, Yunus K Terzi
In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods...
August 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28666104/hematopoietic-cell-transplantation-in-hematological-malignancies-hematopoietic-cell-transplantation-in-acute-myeloid-leukemia
#15
REVIEW
Adetola Kassim, Bipin N Savani
Increasing numbers of patients are receiving allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Scientific and clinical advances in supportive care, donor selection, and conditioning regimens have resulted in lower transplant-related mortality, extension of care to a wider population of patients, and improvements in survival. Recent era has witnessed an explosive information about the molecular pathophysiology of AML. By early identification of patients at a high risk of relapse, it is expected that a majority of eligible patients will receive HCT in first complete remission...
June 20, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28646224/role-of-new-immunophenotypic-markers-on-prognostic-and-overall-survival-of-acute-myeloid-leukemia-a-systematic-review-and-meta-analysis
#16
A F O Costa, D L Menezes, L H S Pinheiro, A F Sandes, M A P Nunes, D P Lyra Junior, D M Schimieguel
Despite technological advances, the prognosis and survival of acute myeloid leukemia (AML) adult patients remain low, compared with other hematologic malignancies. Some antigens detected by immunophenotyping may soon play a significant role in the pathophysiologic, prognostic, and overall survival (OS) rate of AML patients. Therefore, we conducted a systematic review and meta-analysis of PubMed, Scopus, Science Direct, Web of Science, and the Cochrane Library (using PRISMA guidelines). We analyzed 11 studies and 13 antigens, detected through the immunophenotyping of 639 patients...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645565/from-the-outside-from-within-biological-and-therapeutic-relevance-of-signal-transduction-in-t-cell-acute-lymphoblastic-leukemia
#17
REVIEW
Mariana L Oliveira, Padma Akkapeddi, Isabel Alcobia, Afonso R Almeida, Bruno A Cardoso, Rita Fragoso, Teresa L Serafim, João T Barata
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from clonal expansion of transformed T-cell precursors. In this review we summarize the current knowledge on the external stimuli and cell-intrinsic lesions that drive aberrant activation of pivotal, pro-tumoral intracellular signaling pathways in T-cell precursors, driving transformation, leukemia expansion, spread or resistance to therapy. In addition to their pathophysiological relevance, receptors and kinases involved in signal transduction are often attractive candidates for targeted drug development...
June 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28592761/acute-lymphoblastic-leukemia-pathophysiology-and-current-therapy
#18
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
#19
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...
August 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28566565/gata-transcription-factors-basic-principles-and-related-human-disorders
#20
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...
June 2017: Tohoku Journal of Experimental Medicine
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