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https://www.readbyqxmd.com/read/27913502/mrd-in-aml-does-it-already-guide-therapy-decision-making
#1
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
#2
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
#3
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
#4
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
#5
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/27913456/acute-promyelocytic-leukemia-preventing-early-complications-and-late-toxicities
#6
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/27911851/inherited-variants-affecting-rna-editing-may-contribute-to-ovarian-cancer-susceptibility-results-from-a-large-scale-collaboration
#7
Jennifer B Permuth, Brett Reid, Madalene Earp, Y Ann Chen, Alvaro N A Monteiro, Zhihua Chen, Aocs Study Group, Georgia Chenevix-Trench, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Adriaan Vanderstichele, Els Van Niewenhuyse, Ignace Vergote, Mary Anne Rossing, Jennifer Anne Doherty, Jenny Chang-Claude, Kirsten Moysich, Kunle Odunsi, Marc T Goodman, Yurii B Shvetsov, Lynne R Wilkens, Pamela J Thompson, Thilo Dörk, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa Pelttari, Arto Leminen, Francesmary Modugno, Robert P Edwards, Roberta B Ness, Joseph Kelley, Florian Heitz, Beth Karlan, Jenny Lester, Susanne K Kjaer, Allan Jensen, Graham Giles, Michelle Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Douglas A Levine, Maria Bisogna, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Shelley S Tworoger, Elizabeth M Poole, Elisa V Bandera, Brooke Fridley, Julie Cunningham, Stacey J Winham, Sara H Olson, Irene Orlow, Line Bjorge, Lambertus A Kiemeney, Leon Massuger, Tanja Pejovic, Melissa Moffitt, Nhu Le, Linda S Cook, Angela Brooks-Wilson, Linda E Kelemen, Jacek Gronwald, Jan Lubinski, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Hanna Yang, Estrid Hogdall, Claus Hogdall, Lene Lundvall, Paul D P Pharoah, Honglin Song, Ian Campbell, Diana Eccles, Iain McNeish, Alice Whittemore, Valerie McGuire, Weiva Sieh, Joseph Rothstein, Catherine M Phelan, Harvey Risch, Steven Narod, John McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon Gayther, Susan J Ramus, Aleksandra Gentry-Maharaj, Celeste Leigh Pearce, Anna H Wu, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Joellen M Schildkraut, Jin Q Cheng, Ellen L Goode, Thomas A Sellers
RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1...
July 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#8
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
https://www.readbyqxmd.com/read/27911276/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#9
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911138/phase-1-dose-escalation-study-of-oral-abexinostat-for-the-treatment-of-patients-with-relapsed-refractory-higher-risk-myelodysplastic-syndromes-acute-myeloid-leukemia-or-acute-lymphoblastic-leukemia
#10
Norbert Vey, Thomas Prebet, Claire Thalamas, Aude Charbonnier, Jerome Rey, Ioana Kloos, Emily Liu, Ying Luan, Remus Vezan, Thorsten Graef, Christian Recher
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1-14 of 21-day cycles...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910027/recurrent-cytogenetic-abnormalities-in-acute-myeloid-leukemia
#11
John J Yang, Tae Sung Park, Thomas S K Wan
The spectrum of chromosomal abnormality associated with leukemogenesis of acute myeloid leukemia (AML) is broad and heterogeneous when compared to chronic myeloid leukemia and other myeloid neoplasms. Recurrent chromosomal translocations such as t(8;21), t(15;17), and inv(16) are frequently detected, but hundreds of other uncommon chromosomal aberrations from AML also exist. This chapter discusses 22 chromosomal abnormalities that are common structural, numerical aberrations, and other important but infrequent (less than 1 %) translocations emphasized in the WHO classification...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910003/bone-marrow-t-cell-percentage-a-novel-prognostic-indicator-in-acute-myeloid-leukemia
#12
Manar M Ismail, Nahla A B Abdulateef
Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients. We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations. Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City, KSA, from October 2012 to February 2015. Analysis of BM lymphocytes and subpopulations was done by flowcytometry...
December 1, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#13
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27908881/pre-clinical-studies-of-gilteritinib-a-next-generation-flt3-inhibitor
#14
Lauren Y Lee, Daniela Hernandez, Trivikram Rajkhowa, Samuel C Smith, Jayant Ranganathan Raman, Bao Nguyen, Donald Small, Mark Levis
Activating mutations in the receptor tyrosine kinase FLT3 comprise approximately one-third of genetic lesions in acute myeloid leukemia (AML) and are associated with a poor prognosis. Internal tandem duplication (FLT3-ITD) mutations in particular are associated with a high relapse rate. Although FLT3 tyrosine kinase inhibitors (TKIs) appear to improve clinical outcomes for patients with FLT3-ITD AML, the development of early-generation FLT3 TKIs has been impeded by several obstacles such as low potency and selectivity, myelosuppression, and the emergence of resistance-conferring point mutations...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#15
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27908736/cd98-mediated-adhesive-signaling-enables-the-establishment-and-propagation-of-acute-myelogenous-leukemia
#16
Jeevisha Bajaj, Takaaki Konuma, Nikki K Lytle, Hyog Young Kwon, Jailal N Ablack, Joseph M Cantor, David Rizzieri, Charles Chuah, Vivian G Oehler, Elizabeth H Broome, Edward D Ball, Edward H van der Horst, Mark H Ginsberg, Tannishtha Reya
Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient-derived AML, highlighting the importance of this pathway in human disease...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27908660/targeting-of-multiple-senescence-promoting-genes-and-signaling-pathways-by-triptonide-induces-complete-senescence-of-acute-myeloid-leukemia-cells
#17
Yanyan Pan, Mei Meng, Nana Zheng, Zhifei Cao, Ping Yang, Xiaodong Xi, Quansheng Zhou
Leukemia cells aberrantly overexpress senescence-suppression telomerase reverse transcriptase (TERT) and down-regulate key senescence-promoting genes to escape complete senescence, resulting in immortalization and malignant progression. Accordingly, induction of complete senescence is a sensible strategy for anti-leukemia therapy. However, effective senescence-based anti-leukemia drugs with low toxicity are currently lacking. In this study, we found that triptonide (chemical name diterpene triepoxide), a small molecule derived from the herb Tripterygium wilfordii Hook, strongly induced complete senescence in cultured acute myeloid leukemia (AML) cell lines, and potently inhibited growth and colony formation of U937 and HL-60 AML cell line with IC50 values of 7...
November 28, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27906794/health-related-quality-of-life-hr-qol-and-chronic-health-conditions-in-survivors-of-childhood-acute-myeloid-leukemia-aml-with-down-syndrome-ds-a-report-from-the-children-s-oncology-group
#18
Kris Ann P Schultz, Lu Chen, Alicia Kunin-Batson, Zhengjia Chen, William G Woods, Alan Gamis, Toana Kawashima, Kevin C Oeffinger, H Stacy Nicholson, Joseph P Neglia
Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8...
November 30, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27906458/autologous-stem-cell-transplantation-for-adult-acute-myelocytic-leukemia-in-first-remission-better-outcomes-after-busulfan-and-melphalan-compared-with-busulfan-and-cyclophosphamide-a-retrospective-study-from-the-acute-leukemia-working-party-of-the-european
#19
Norbert-Claude Gorin, Myriam Labopin, Tomasz Czerw, Thomas Pabst, Didier Blaise, Pierre-Yves Dumas, Damir Nemet, William Arcese, Silvia Maria Trisolini, Depei Wu, Anne Huynh, Tsila Zuckerman, Ellen Meijer, Seckin Cagirgan, Jan Cornelissen, Mohamed Houhou, Emmanuelle Polge, Mohamad Mohty, Arnon Nagler
BACKGROUND: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27906185/anti-proliferative-activity-of-the-npm1-interacting-natural-product-avrainvillamide-in-acute-myeloid-leukemia
#20
Vibeke Andresen, Bjarte S Erikstein, Herschel Mukherjee, André Sulen, Mihaela Popa, Steinar Sørnes, Håkon Reikvam, Kok-Ping Chan, Randi Hovland, Emmet McCormack, Øystein Bruserud, Andrew G Myers, Bjørn T Gjertsen
Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1...
December 1, 2016: Cell Death & Disease
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