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acute leukemia pathophysiology

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https://www.readbyqxmd.com/read/28802867/novel-single-cell-technologies-in-acute-myeloid-leukemia-research
#1
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...
July 25, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28515935/methotrexate-encephalopathy-two-cases-in-adult-cancer-patients-who-recovered-with-pathophysiologically-based-therapy
#10
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
#11
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
#12
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
#13
MULTICENTER STUDY
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)...
July 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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