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Leukemia Research

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https://www.readbyqxmd.com/read/29149650/iron-chelation-therapy-in-lower-ipss-risk-myelodysplastic-syndromes-which-subtypes-benefit
#1
Shannon A Wong, Heather A Leitch
BACKGROUND: Analyses suggest MDS patients with higher serum ferritin levels (SF) have inferior overall survival (OS), in one study across MDS subtypes. Multiple analyses suggest those with high SF receiving iron chelation therapy (ICT) have superior OS, but which MDS subtypes benefit from ICT remains undefined. METHODS: We performed survival analyses of MDS subtypes by receipt of ICT. RESULTS: 182 MDS were lower IPSS risk and received red blood cell (RBC) transfusions; 63 received ICT...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149649/chk1-inhibitors-overcome-imatinib-resistance-in-chronic-myeloid-leukemia-cells
#2
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29144985/a-phase-1-2-study-of-rigosertib-in-patients-with-myelodysplastic-syndromes-mds-and-mds-progressed-to-acute-myeloid-leukemia
#3
Shyamala C Navada, Steven M Fruchtman, Rosalie Odchimar-Reissig, Erin P Demakos, Michael E Petrone, Patrick S Zbyszewski, James F Holland, Lewis R Silverman
This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m(2)/day in 14-day cycles...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29132010/inhibition-of-sonic-hedgehog-signaling-blocks-cell-migration-and-growth-but-induces-apoptosis-via-suppression-of-foxq1-in-natural-killer-t-cell-lymphoma
#4
Pingyi Liu, Lingling Chen
The present study explored the effects of Forkhead box Q1 (FOXQ1) on cell proliferation, cell cycle and apoptosis via the Sonic hedgehog (Shh) pathway in Natural killer/T-cell lymphoma (NKTCL). Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect FOXQ1 expression in 117 NKTCL patients and 120 healthy controls. Additionally, FOXQ1 expression in NKTCL cell lines (HANK-1, NK-92, SNK-6, SNT-8 and YT) was determined by western blotting and qRT-PCR. SNK-6 cells were transfected with FOXQ1-shRNA or Shh pathway inhibitor Cyclopamine/recombinant protein Shh...
November 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29127862/frondoside-a-potentiates-the-effects-of-conventional-therapeutic-agents-in-acute-leukemia
#5
F H Sajwani, P Collin, T E Adrian
Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy...
November 8, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29127861/altered-ezh2-splicing-and-expression-is-associated-with-impaired-histone-h3-lysine-27-tri-methylation-in-myelodysplastic-syndrome
#6
Mizuho Shirahata-Adachi, Chisako Iriyama, Akihiro Tomita, Yasuhiro Suzuki, Kazuyuki Shimada, Hitoshi Kiyoi
BACKGROUND: EZH2 (enhancer of zeste homolog 2) is a histone H3K27 methyltransferase involved in the pathogenesis of various hematological malignancies. In myelodysplastic syndromes (MDS), loss of function of EZH2 is known to contribute to pathogenesis, however the pattern of EZH2 mRNA and protein expression in MDS has not been extensively characterized. MATERIAL AND METHODS: A total of 26 patients diagnosed with MDS were analyzed in this study. The relationship between EZH2 expression in patient bone marrow samples, evaluated by RT-PCR and immunoblotting, and patient characteristics were analyzed...
November 4, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29102597/predictors-for-requiring-re-induction-chemotherapy-in-acute-myeloid-leukemia-patients-with-residual-disease-on-day-14-bone-marrow-assessment
#7
Victoria R Nachar, Anthony J Perissinotti, Gianni B Scappaticci, Dale L Bixby, Bernard L Marini
PURPOSE: Day 14 bone marrow (BM) biopsies following standard induction in acute myeloid leukemia (AML) have a suboptimal ability to predict complete remission (CR). The decision to administer re-induction chemotherapy with residual disease on day 14 is variable and lacks clear guidance. METHODS: We retrospectively compared clinical and laboratory characteristics of adult patients with newly diagnosed, previously untreated AML who underwent 3+7 induction chemotherapy from January 2004 until February 2017...
November 2, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29101827/differential-t-cell-subsets-and-cytokine-profile-between-steady-state-and-g-csf-primed-bone-marrow-and-its-association-with-graft-versus-host-disease
#8
Eucario León-Rodríguez, Monica M Rivera-Franco, Diana Gómez-Martín, Jorge Romo-Tena, Guillermo Juárez-Vega, Javier Merayo-Chalico, Jorge Alcocer-Varela
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). At our Institution, patients transplanted using G-CSF-primed bone marrow (G-BM), have a lower incidence of GVHD when compared to other sources. The objective of this study was to analyze and compare T cell subsets and cytokines in donor G-BM and steady-state BM (SS-BM). A prospective study was performed in 48 donor samples. Mononuclear cells were isolated by gradient density. T cell subsets and cytokine production in supernatants were analyzed by multiparametric flow cytometry...
November 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29102598/dicer1-gene-and-mirna-dysregulation-in-mesenchymal-stem-cells-of-patients-with-myelodysplastic-syndrome-and-acute-myeloblastic-leukemia
#9
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/29101828/jak2-v617f-detection-and-allele-burden-measurement-in-saliva-vs-peripheral-blood-in-patients-with-myelofibrosis
#10
Paolo Strati, Christopher B Benton, Taghi Manshouri, Ying Zhang, Joseph E Bove, Gabriela Sanchez-Petitto, Srdan Verstovsek
We previously demonstrated that peripheral blood (PB) is a reliable source for testing JAK2(V617F) mutation in patients with myelofibrosis (MF); saliva has also been tested to detect such mutation, however its diagnostic accuracy as compared to PB has not been validated. In this study, we prospectively tested 167 patients with MF for JAK2(V617F) mutation, using both saliva and PB collected at the same time from each patient. The concordance between the 2 sources was 96%, with a sensitivity of 100% and a specificity of 90%...
October 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29121539/clinical-and-biological-significance-of-isolated-y-chromosome-loss-in-myelodysplastic-syndromes-and-chronic-myelomonocytic-leukemia-a-report-from-the-spanish-mds-group
#11
Meritxell Nomdedeu, Arturo Pereira, Xavier Calvo, Joan Colomer, Francesc Sole, Amparo Arias, Candida Gomez, Elisa Luño, Jose Cervera, Montserrat Arnan, Helena Pomares, Fernando Ramos, Itziar Oiartzabal, Blanca Espinet, Carme Pedro, Beatriz Arrizabalaga, María Laura Blanco, Mar Tormo, Jesus Maria Hernandez-Rivas, María Díez-Campelo, Margarita Ortega, David Valcárcel, Maria-Teresa Cedena, Rosa Collado, Javier Grau, Isabel Granada, Guillermo Sanz, Elias Campo, Jordi Esteve, Dolors Costa
Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML)...
October 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29100024/towards-repositioning-of-quinacrine-for-treatment-of-acute-myeloid-leukemia-promising-synergies-and-in-vivo-effects
#12
Anna Eriksson, Efthymia Chantzi, Mårten Fryknäs, Joachim Gullbo, Peter Nygren, Mats Gustafsson, Martin Höglund, Rolf Larsson
We previously reported that the anti-malarial drug quinacrine has potential to be repositioned for treatment of acute myeloid leukemia (AML). As a next step towards clinical use, we assessed the efficacy of quinacrine in an AML-PS mouse model and investigated possible synergistic effects when combining quinacrine with nine other antileukemic compounds in two AML cell lines. Furthermore, we explored the in vivo activity of quinacrine in combination with the widely used AML agent cytarabine. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST)...
October 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29121538/therapeutic-options-for-leukemic-transformation-in-patients-with-myeloproliferative-neoplasms
#13
REVIEW
Maliha Khan, Rabbia Siddiqi, Naseema Gangat
Approximately 5-10% of patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprising of essential thrombocythemia, polycythemia vera and primary myelofibrosis) experience transformation to acute myeloid leukemia (AML, ≥20% blasts). Treatment options for post-MPN AML patients are limited, as conventional approaches like standard chemotherapy, fail to offer long-term benefit. Median survival for secondary AML is ∼2.4 months. Post-MPN AML therefore represents an area of urgent clinical need...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29112938/impact-of-baseline-cytogenetic-findings-and-cytogenetic-response-on-outcome-of-high-risk-myelodysplastic-syndromes-and-low-blast-count-aml-treated-with-azacitidine
#14
Marie Sébert, Rami S Komrokji, Mikkael A Sekeres, Thomas Prebet, Thomas Cluzeau, Valeria Santini, Emmanuel Gyan, Alessandro Sanna, Najla HAl Ali, Sean Hobson, Virginie Eclache, Alan List, Pierre Fenaux, Lionel Adès
Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#15
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096332/high-prognostic-value-of-pre-allogeneic-stem-cell-transplantation-minimal-residual-disease-detection-by-wt1-gene-expression-in-aml-transplanted-in-cytologic-complete-remission
#16
Anna Candoni, Federico De Marchi, Maria Elena Zannier, Davide Lazzarotto, Carla Filì, Maria Vittoria Dubbini, Nicholas Rabassi, Eleonora Toffoletti, Bonnie W Lau, Renato Fanin
We analyzed the outcome of allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML) patients according to molecular Minimal Residual Disease (MRD) status prior to allo-SCT. MRD was assessed by the quantitative expression of the pan-leukemic marker Wilms' tumor (WT1) gene, according to the validated LeukemiaNet method. Between 2005 and 2016, 122 consecutive AML patients, WT1 positive at diagnosis, received allo-SCT in cytologic complete remission (cCR). The median age at SCT was 53 years (range 18-70)...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096331/nucleostemin-silencing-induces-differentiation-and-potentiates-all-trans-retinoic-acid-effects-in-human-acute-promyelocytic-leukemia-nb4-cells-via-autophagy
#17
Aila Fakhimahmadi, Farinaz Nazmi, Marveh Rahmati, Nazila Moghtaran Bonab, Mehrdad Hashemi, Mohammad Amin Moosavi
Here, we report that targeting Nucleostemin (NS), a recently discovered stem cells-enriched gene, by a specific small interference RNA (siNS), decreases the rate of proliferation of acute promyelocytic leukemia (APL) NB4 cells and induces differentiation and autophagy. In addition, NS silencing promotes the effects of all-trans-retinoic acid (ATRA)-based differentiation therapy in NB4 cells. Autophagy inhibitors 3-methyladenine and bafilomycin block the effect of NS targeting on differentiation, indicating a new functional link between NS and autophagy as an important regulator of differentiation in NB4 cells...
October 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29078080/relationship-between-lenalidomide-dose-modification-duration-of-therapy-and-long-term-outcomes-in-patients-with-myelodysplastic-syndromes
#18
Amy E DeZern, Gary Binder, Quanhong Ni, Michael McGuire, B Douglas Smith
Dose reductions or interruptions may be required to manage treatment-associated adverse events among patients with myelodysplastic syndromes (MDS) treated with lenalidomide; such modifications are recommended to sustain therapy and maximize treatment duration. The aim of this retrospective case-control study was to determine the relationship between lenalidomide dose modification (DM), duration of lenalidomide therapy (DOT), and patient outcomes in patients with MDS. Those patients with database follow-up >20months (n=305) were more likely to have received erythropoiesis-stimulating agents (ESAs) (P=0...
October 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29055789/in-vitro-studies-on-the-role-of-recombinant-human-soluble-thrombomodulin-in-the-context-of-retinoic-acid-mediated-apl-differentiation-syndrome
#19
Shinsuke Kojima, Chie Nishioka, SungGi Chi, Akihito Yokoyama, Takayuki Ikezoe
Recombinant human soluble thrombomodulin (rTM) is a newly developed anti-coagulant approved for treatment of disseminated intravascular coagulation (DIC) in Japan. rTM exerts anti-inflammatory and cytoprotective functions via its lectin-like and epidermal growth factor-like domains, respectively. In this study, we retrospectively reviewed the treatment of 21 consecutive patients with coagulopathy, complicated by acute promyelocytic leukemia (APL), with all-trans retinoic acid (ATRA) with or without combination with rTM...
October 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096334/symptom-burden-profile-in-myelofibrosis-patients-with-thrombocytopenia-lessons-and-unmet-needs
#20
Allison H Scotch, Heidi Kosiorek, Robyn Scherber, Amylou C Dueck, Stefanie Slot, Sonja Zweegman, Peter A W Te Boekhorst, Suzan Commandeur, Harry Schouten, Federico Sackmann, Ana Kerguelen Fuentes, Dolores Hernández-Maraver, Heike L Pahl, Martin Griesshammer, Frank Stegelmann, Konstanze Döhner, Thomas Lehmann, Karin Bonatz, Andreas Reiter, Francoise Boyer, Gabriel Etienne, Jean-Christophe Ianotto, Dana Ranta, Lydia Roy, Jean-Yves Cahn, Claire N Harrison, Deepti Radia, Pablo Muxi, Norman Maldonado, Carlos Besses, Francisco Cervantes, Peter L Johansson, Tiziano Barbui, Giovanni Barosi, Alessandro M Vannucchi, Chiara Paoli, Francesco Passamonti, Bjorn Andreasson, Maria L Ferrari, Alessandro Rambaldi, Jan Samuelsson, Gunnar Birgegard, Zhijian Xiao, Zefeng Xu, Yue Zhang, Xiujuan Sun, Junqing Xu, Jean-Jacques Kiladjian, Peihong Zhang, Robert Peter Gale, Ruben A Mesa, Holly L Geyer
Myelofibrosis is a myeloproliferative neoplasm associated with progressive cytopenias and high symptom burden. MF patients with thrombocytopenia have poor prognosis but the presence of thrombocytopenia frequently precludes the use of JAK2 inhibitors. In this study, we assessed quality of life and symptom burden in 418 MF patients with (n=89) and without (n=329) thrombocytopenia using prospective data from the MPN-QOL study group database, including the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and Total Symptom Score (MPN10)...
October 14, 2017: Leukemia Research
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