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Leukemia treatment

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https://www.readbyqxmd.com/read/28646646/antileukemic-activity-and-cellular-effects-of-the-antimalarial-agent-artesunate-in-acute-myeloid-leukemia
#1
Bijender Kumar, Arjun Kalvala, Su Chu, Steven Rosen, Stephen J Forman, Guido Marcucci, Ching-Cheng Chen, Vinod Pullarkat
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients' blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics...
May 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28646624/prognostic-relevance-of-oxidative-stress-measurement-in-chronic-lymphocytic-leukemia
#2
Giovanni D'Arena, Candida Vitale, Omar Perbellini, Marta Coscia, Francesco La Rocca, Vitalba Ruggieri, Carlo Visco, Matteo Nicola Dario Di Minno, Idanna Innocenti, Vincenzo Pizza, Silvia Deaglio, Giovanni Di Minno, Aldo Giudice, Gioacchino Calapai, Pellegrino Musto, Luca Laurenti, Eugenio Luigi Iorio
OBJECTIVE: To evaluate the prognostic significance of oxidative stress (OS) and antioxidant defense status measurement in patients with chronic lymphocytic leukemia (CLL). METHOD: d-ROMs test and BAP test were evaluated at diagnosis of 165 patients with CLL and correlated with clinical-biological features and prognosis. RESULTS: An increased oxidative damage (d-ROMs test) and a reduced antioxidant potential (BAP test), were found in CLL patients than normal controls (p <0...
June 24, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28646488/mutation-in-the-fgfr1-tyrosine-kinase-domain-or-inactivation-of-pten-is-associated-with-acquired-resistance-to-fgfr-inhibitors-in-fgfr1-driven-leukemia-lymphomas
#3
John K Cowell, Haiyan Qin, Tianxiang Hu, Qing Wu, Aaron Bhole, Mingqiang Ren
Stem cell leukemia/lymphoma syndrome (SCLL) is driven by constitutive activation of chimeric FGFR1 kinases generated by chromosome translocations. We have shown that FGFR inhibitors significantly suppress leukemia and lymphoma development in vivo, and cell viability in vitro. Since resistance to targeted therapies is a major reason for relapse, we developed FGFR1-overexpressing mouse and human cell lines that are resistant to the specific FGFR inhibitors AZD4547 and BGJ398, as well as non-specific inhibitors, such as ponatinib, TKI258 and E3810...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#4
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28646023/amlexanox-downregulates-s100a6-to-sensitize-kmt2a-aff1-positive-acute-lymphoblastic-leukemia-to-tnf-%C3%AE-treatment
#5
Hayato Tamai, Hiroki Yamaguchi, Koichi Miyake, Miyuki Takatori, Tomoaki Kitano, Satoshi Yamanaka, Syunsuke Yui, Keiko Fukunaga, Kazutaka Nakayama, Koiti Inokuchi
Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This poor prognosis is due to one of two factors, either resistance to TNF-α which mediates a graft-versus-leukemia (GVL) response after allo-HSCT, or immune resistance due to upregulated expression of the immune escape factor S100A6. Here we report an immune stimulatory effect against KMT2A/AFF1-positive ALL cells by treatment with the anti-allergy drug amlexanox, which we found to inhibit S100A6 expression in the presence of TNF-α...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645939/combined-btk-and-pi3k%C3%AE-inhibition-with-acalabrutinib-and-acp-319-improves-survival-and-tumor-control-in-cll-mouse-model
#6
Carsten U Niemann, Helena I Mora-Jensen, Eman L Dadashian, Fanny Krantz, Todd Covey, Shih-Shih Chen, Nicholas- Chiorazzi, Raquel Izumi, Roger Ulrich, Brian J Lannutti, Adrian Wiestner, Sarah E M Herman
Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#7
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#8
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28645468/aldhs-in-normal-and-malignant-hematopoietic-cells-potential-new-avenues-for-treatment-of-aml-and-other-blood-cancers
#9
Maura Gasparetto, Clayton A Smith
Multiple studies have demonstrated that ALDH1A1 is elevated in hematopoietic stem cells (HSCs). As a means to better characterize such cells, we previously developed the fluorescent ALDH1A1 substrate Aldefluor to facilitate HSC identification and isolation. This has proven useful for counting and isolating HSCs from human bone marrow, peripheral blood and cord blood as well as stem cells in other tissues and organisms. Given the high level expression of ALDH1A1, we explored its biology and that of other ALDHs in HSCs and found that ALDH1A1 and ALDH3A1 were important in metabolizing reactive aldehydes (RAlds) and reactive oxygen species (ROS)...
June 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28645262/acute-myeloid-leukemia-and-pregnancy-clinical-experience-from-a-single-center-and-a-review-of-the-literature
#10
Nicola Stefano Fracchiolla, Mariarita Sciumè, Francesco Dambrosi, Francesca Guidotti, Manuela Wally Ossola, Giovanna Chidini, Umberto Gianelli, Daniela Merlo, Agostino Cortelezzi
BACKGROUND: Acute myeloid leukemia (AML) accounts for more than two thirds of leukemia during pregnancy and has an incidence of 1 in 75,000 to 100,000. Its clinical management remains a challenging therapeutic task both for patient and medical team, given to the therapy-attributable risks for mother and fetus and the connected counseling regarding pregnancy continuation. METHODS: We provided a review of updated literature and a comprehensive description of five maternal/fetal outcomes of AML cases diagnosed concomitantly to pregnancy and treated at our Institution from 2006 to 2012...
June 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28644949/hematopoietic-cell-transplantation-for-acute-lymphoblastic-leukemia-in-adult-patients
#11
REVIEW
Riad El Fakih, Syed Ahmed, Feras Alfraih, Amr Hanbali
Acute lymphoblastic leukemia (ALL) consists of precursor B ALL or T ALL phenotypes. In the pediatric population, ALL patients enjoy an 80% long-term survival with the current pediatric chemotherapy protocols as compared with 50% long-term survival in the adult population. In adults, complete remission rates are similar to those of pediatric patients; however, long-term survival is much lower with the majority of deaths attributable to relapsed disease. Postremission consolidation strategies in adults include chemotherapy, autologous, or allogeneic transplant...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28644853/the-novel-phospholipid-mimetic-kpc34-is-highly-active-against-preclinical-models-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#12
Peter M Alexander, David L Caudell, Gregory L Kucera, Kristin M Pladna, Timothy S Pardee
Philadelphia chromosome positive B cell acute lymphoblastic leukemia (Ph+ ALL) is an aggressive cancer of the bone marrow. The addition of tyrosine kinase inhibitors (TKIs) has improved outcomes but many patients still suffer relapse and novel therapeutic agents are needed. KPC34 is an orally available, novel phospholipid conjugate of gemcitabine, rationally designed to overcome multiple mechanisms of resistance, inhibit the classical and novel isoforms of protein kinase C, is able to cross the blood brain barrier and is orally bioavailable...
2017: PloS One
https://www.readbyqxmd.com/read/28644773/mobilized-peripheral-blood-stem-cells-versus-unstimulated-bone-marrow-as-a-graft-source-for-t-cell-replete-haploidentical-donor-transplantation-using-post-transplant-cyclophosphamide
#13
Asad Bashey, Mei-Jie Zhang, Shannon R McCurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen
Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#14
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas Covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28644156/clinical-case-of-the-month-a-57-year-old-man-with-an-axillary-mass
#15
Palak Desai, Andrew Myers, Brian Boulmay, Fred A Lopez
A 57-year-old man presented to the surgical oncology clinic with a mildly tender mass under his right arm. Four years prior, the patient had a melanoma removed from his right shoulder along with an ipsilateral right axillary sentinel lymph sampling. Computed tomography (CT) scan was negative for metastatic disease at that time. The patient did not undergo completion axillary node dissection and was lost to follow-up. The patient was originally from Australia, did not tan but reported multiple sunburns before age 18...
May 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28644154/acute-promyelocytic-leukemia-and-chronic-lymphocytic-leukemia-concomitant-presentation-of-two-molecularly-distinct-entities
#16
Jingdong Su, Diana Veillon, Rodney Shackelford, James Cotelingam, Hazem El-Osta, Glenn Mills, Reinhold Munker, Srinivas Devarakonda
Acute myeloid leukemia (AML) developing in patients with chronic lymphocytic leukemia (CLL) is very uncommon and usually associated with prior treatment. Acute promyelocytic leukemia (APL) accounts for a very small proportion of treatment-associated AML. So far, there has been only one reported case of APL occurring post radiation for prostate cancer in a patient with CLL. We report herein the first case of APL and CLL presenting concomitantly in an untreated patient. Evaluation of peripheral blood and bone marrow aspirate with immunohistochemistry, flow cytometry, and FISH to confirm two morphologically, molecularly and genetically distinct leukemic populations characteristic of APL and CLL is required...
May 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28644114/midostaurin-plus-chemotherapy-for-acute-myeloid-leukemia-with-a-flt3-mutation
#17
Richard M Stone, Sumithra J Mandrekar, Ben L Sanford, Kristina Laumann, Susan Geyer, Clara D Bloomfield, Christian Thiede, Thomas W Prior, Konstanze Döhner, Guido Marcucci, Francesco Lo-Coco, Rebecca B Klisovic, Andrew Wei, Jorge Sierra, Miguel A Sanz, Joseph M Brandwein, Theo de Witte, Dietger Niederwieser, Frederick R Appelbaum, Bruno C Medeiros, Martin S Tallman, Jürgen Krauter, Richard F Schlenk, Arnold Ganser, Hubert Serve, Gerhard Ehninger, Sergio Amadori, Richard A Larson, Hartmut Döhner
Background Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. Methods We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo...
June 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28643684/-adult-t-cell-leukemia-lymphoma-report-of-a-case-in-uruguay
#18
Matilde Boada, Sofía Grille, Andreina Brugnini, Natalia Trias, Cecilia Canesa, Lilián Díaz, Daniela Lens
Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement...
2017: Medicina
https://www.readbyqxmd.com/read/28643670/-chronic-myelogenous-leukemia-monitoring-and-predictors-of-a-favorable-response-to-treatment-with-imatinib
#19
María J Mela Osorio, Isabel A Giere, Isolda Fernández, Miguel A Pavlovsky, Dante Intile, Carolina Pavlovsky
The expected five-year survival of chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors is over 90%. Little data is available regarding the results in the Argentinian population. This information might be of interest as generic imatinib is now available in the region. The aim of this study is to provide information on monitoring and the long-term treatment with imatinib outside of a controlled clinical trial, as well as to analyze the predictive effect of early responses to achieve molecular remission 4...
2017: Medicina
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#20
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
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