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Acute myeloid leukemia

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https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#1
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27920142/shedding-light-on-fat-dependence-in-aml
#2
(no author information available yet)
Scientists have begun unraveling the molecular intricacies that drive the appetite of acute myeloid leukemia for fat. They found that these tumor cells have particularly low levels of PHD3, an enzyme that normally activates ACC2 to repress fatty-acid oxidation. This fuels the cells' metabolic reliance on fat-burning, but also renders them highly susceptible to inhibitors of fatty-acid oxidation.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27919943/kinomics-screening-identifies-aberrant-phosphorylation-of-cdc25c-in-flt3-itd-positive-aml
#3
Florian Perner, Tina M Schnöder, Thomas Fischer, Florian H Heidel
BACKGROUND/AIM: The presence of FLT3-Internal tandem duplications (ITDs) in human acute myeloid leukemia (AML) is associated with a dismal prognosis. Altered cell-cycle activity has been reported in FLT3-ITD-positive AML; however, the mechanisms by which this oncogene influences cell-cycle activity remained so far elusive. MATERIALS AND METHODS: A phospho-kinomic screen was used to identify downstream effectors of FLT3-ITD. Validation and functional characterization was performed by western blotting, cell-cycle analysis and apoptosis assays...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27917176/graft-immune-cell-composition-associates-with-clinical-outcome-of-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aml
#4
Ulla Impola, Antti Larjo, Urpu Salmenniemi, Mervi Putkonen, Maija Itälä-Remes, Jukka Partanen
Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27917123/mir-150-suppresses-the-proliferation-and-tumorigenicity-of-leukemia-stem-cells-by-targeting-the-nanog-signaling-pathway
#5
Dan-Dan Xu, Peng-Jun Zhou, Ying Wang, Yi Zhang, Rong Zhang, Li Zhang, Su-Hong Chen, Wu-Yu Fu, Bi-Bo Ruan, Hai-Peng Xu, Chao-Zhi Hu, Lu Tian, Jin-Hong Qin, Sheng Wang, Xiao Wang, Qiu-Ying Liu, Zhe Ren, Xue-Kui Gu, Yao-He Li, Zhong Liu, Yi-Fei Wang
Proliferation, a key feature of cancer cells, accounts for the majority of cancer-related diseases resulting in mortality. MicroRNAs (miRNAs) plays important post-transcriptional modulation roles by acting on multiple signaling pathways, but the underlying mechanism in proliferation and tumorigenicity is unclear. Here, we identified the role of miR-150 in proliferation and tumorigenicity in leukemia stem cells (LSCs; CD34+CD38- cells). miR-150 expression was significantly down-regulated in LSCs from leukemia cell lines and clinical samples...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27916717/is-luks-pv-a-novel-experimental-therapy-for-leukemia
#6
REVIEW
Wulin Shan, Xiaoling Ma, Fang Deng
Although the studies on the pathogenesis and prognosis of leukemia have made revolutionary progress, the long-term survival remains unsatisfactory. Alternative techniques are being developed to target leukemia. Several decades after researchers' work, a variety of bacteria toxins are being explored as potential anti-leukemia agents, either to provide direct effects or to deliver therapeutic proteins to leukemia. LukS-PV, a component of Panton-Valentine Leukocidin secreted by S. aureus, has been tested in acute myeloid leukemia as a novel experimental strategy...
December 1, 2016: Gene
https://www.readbyqxmd.com/read/27916548/high-expression-of-cpt1a-predicts-adverse-outcomes-a-potential-therapeutic-target-for-acute-myeloid-leukemia
#7
Jinlong Shi, Huaping Fu, Zhilong Jia, Kunlun He, Lin Fu, Weidong Wang
Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1A(low)), high expression of CPT1A (CPT1A(high)) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category...
November 22, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27916512/impact-of-conditioning-regimen-on-outcomes-for-children-with-acute-myeloid-leukemia-transplanted-in-first-complete-remission-an-analysis-on-behalf-of-the-pediatric-disease-working-party-of-the-ebmt
#8
G Lucchini, M Labopin, E Beohou, A Dalissier, J H Dalle, J Cornish, M Zecca, S Samarasinghe, B Gibson, F Locatelli, Y Bertrand, F Abdel-Rahman, G Socie', M Sundin, A Lankester, P Sedlacek, R M Hamladji, C Heilmann, B Afanasyev, R Hough, C Peters, P Bader, P Veys
HSCT represents the cornerstone of treatment in pediatric high risk and relapsed AML. The aim of the present study was to compare outcomes of pediatric AML patients undergoing HSCT using three different conditioning regimens: TBI and cyclophosphamide (TBI-Cy), Busulfan and Cyclophosphamide (BuCy) or Busulfan, Cyclophosphamide and Melphalan (BuCyMel). In this retrospective study, registry data for pts>2 and <18 yrs age undergoing matched allogeneic HSCT for AML in CR1 in 204 EBMT Centres between 2000 and 2010 were analyzed...
December 1, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27915304/invasive-aspergillosis-in-acute-myeloid-leukemia-are-we-making-progress-in-reducing-mortality
#9
Giulia Dragonetti, Marianna Criscuolo, Luana Fianchi, Livio Pagano
The incidence of invasive fungal disease (IFD) has varied during the last decades. However, over the years, we have observed a progressive reduction of mortality, mainly due to wider use of prophylactic antifungal therapy (i.e., new azoles, such as posaconazole), the development of new and more effective antifungal drugs (lipid compounds of amphotericin B, candins, and azoles of the previous generation) and improvement of diagnostic tools. Based on a number of international studies across three decades, the attributable mortality rate for IFD and invasive aspergillosis (IA) among patients with acute myeloid leukemia (AML) has progressively declined...
December 2, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27914102/examining-temporal-effects-on-cancer-risk-in-the-international-nuclear-workers-study-inworks
#10
Robert D Daniels, Stephen J Bertke, David B Richardson, Elisabeth Cardis, Michael Gillies, Jacqueline A O'Hagan, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Isabelle Thierry-Chef, Ausrele Kesminiene, Mary K Schubauer-Berigan
The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure...
December 3, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#11
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#12
Gert Ossenkoppele, Gerrit Jan Schuurhuis
Prognostic factors determined at diagnosis are predictive for outcome whereas achievement of morphological complete remission (CR) is still an important end point during treatment. Residual disease after therapy may reflect the sum of all diagnosis and postdiagnosis resistance mechanisms/factors; its measurement could hypothetically be very instrumental for guiding treatment. The possibility of defining residual disease (minimal residual disease [MRD]) far below the level of 5% blast cells is changing the landscape of risk classification...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913501/mutations-in-aml-prognostic-and-therapeutic-implications
#13
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/27913500/fitness-in-the-elderly-how-to-make-decisions-regarding-acute-myeloid-leukemia-induction
#14
Arati V Rao
Acute myeloid leukemia (AML) is a disease of the elderly, but less than half of these patients are offered therapy despite the evidence of better survival with treatment in this patient population. Assessing fit, vulnerable, and frail older adults with AML remains a challenge for the treating oncologist. A majority of AML patients are elderly and often have significant comorbidities, lack of social support, and older caregivers. Performance status (PS), a subjective measure of how a patient will tolerate cancer chemotherapy, has been strongly correlated with mortality in older AML patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913465/aplastic-anemia-and-clonal-evolution-germ-line-and-somatic-genetics
#15
Akiko Shimamura
Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913458/therapy-related-myeloid-neoplasms-does-knowing-the-origin-help-to-guide-treatment
#16
Michael Heuser
Therapy-related myeloid neoplasms (t-MN) combine t-MDS and therapy related acute myeloid leukemia (t-AML) patients in one entity because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. Treatment with epipodophyllotoxins like etoposide has been associated with a short interval between treatment and development of t-AML, with fusion oncogenes like KMT2A/MLL-MLLT3 and a better prognosis. In contrast, treatment with alkylating agents has been associated with a longer latency, an initial MDS phase, adverse cytogenetics, and a poor prognosis...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913457/treatment-of-blastic-plasmacytoid-dendritic-cell-neoplasm
#17
Jill M Sullivan, David A Rizzieri
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4(+)CD56(+)CD123(+)lineage(-)MPO(-), although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913456/acute-promyelocytic-leukemia-preventing-early-complications-and-late-toxicities
#18
Sameem Abedin, Jessica K Altman
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913051/erg-expression-in-multiple-myeloma-a-potential-diagnostic-pitfall
#19
Juliana Knief, Katharina Reddemann, Jan Gliemroth, Swantje Brede, Tobias Bartscht, Christoph Thorns
INTRODUCTION: ERG expression has been described as a frequent event in prostate cancer indicating poor prognosis and promoting oncogenesis. It has also been demonstrated in Ewing's sarcoma, acute myeloid leukemia and acute T-lymphoblastic leukemia but could not be found in other epithelial tumors, Hodgkin's or Non-Hodgkin's lymphoma. We aimed to analyze ERG expression in multiple myeloma, following an index case of a patient with metastases of unknown origin in the spine strongly expressing ERG, which were thought to be of prostatic origin but turned out to be plasmacytic lesions...
November 3, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#20
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
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