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Acute myelogenous leukemia

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https://www.readbyqxmd.com/read/28329516/precursor-b-cell-all-leukemia-cutis-resembling-lipomas-an-atypical-presentation-of-a-rare-entity-and-a-review-of-the-literature
#1
Yuan Yu Michael Huang, Melinda Liu, Jennifer S Ruth, Silvia Potenziani, Sylvia Hsu
Leukemia cutis (LC) is an extramedullary manifestationof leukemia owing to cutaneous infiltration ofneoplastic cells resulting in characteristic firm,erythematous nodules. Most cases of LC occur inpatients with acute myelogenous leukemia andchronic myelogenous leukemia. However in rarecases, LC has presented in patients with acutelymphoblastic leukemia (ALL). In these rare ALLassociatedcases, only 10 cases of precursor-B-ALL(pre-B-ALL) have been described in the literature.We report a case of a 22-year-old man with relapsingpre-B-ALL who presented with a 4-day history ofmultiple asymptomatic, soft, dome-shaped, lipomalikemounds on his scalp and chin, which exhibitedcutaneous involvement by leukemic cells...
March 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28297583/assessment-of-drug-sensitivity-in-hematopoietic-stem-and-progenitor-cells-from-acute-myelogenous-leukemia-and-myelodysplastic-syndrome-ex-vivo
#2
Katherine L B Knorr, Laura E Finn, B Douglas Smith, Allan D Hess, James M Foran, Judith E Karp, Scott H Kaufmann
Current understanding suggests that malignant stem and progenitor cells must be reduced or eliminated for prolonged remissions in myeloid neoplasms such as acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Multicolor flow cytometry has been widely used to distinguish stem and myeloid progenitor cells from other populations in normal and malignant bone marrow. In this study, we present a method for assessing drug sensitivity in MDS and AML patient hematopoietic stem and myeloid progenitor cell populations ex vivo using the investigational Nedd8-activating enzyme inhibitor MLN4924 and standard-of-care agent cytarabine as examples...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28278270/methylation-level-of-cpg-islands-in-ggh-gene-promoter-in-pediatric-acute-leukemia
#3
Yue Li, Sixi Liu, Huihui Wang, Huirong Mai, Xiuli Yuan, Changgang Li, Xiaowen Chen, Feiqiu Wen
BACKGROUND: γ-Glutamyl hydrolase (GGH) regulates intracellular folates and antifolates such as methotrexate (MTX) for proper nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. In addition to genetic polymorphism and karyotypic abnormalities, methylation of CpG island 1 (CpG1) in the promoter region is found to modulate GGH activity by reducing GGH mRNA expression in acute lymphoblastic leukemia (ALL) cells. We aim to investigate methylation status of two CpG islands (CpG1 and CpG2) in the GGH promoter region in pediatric patients with ALL and acute myelogenous leukemia (AML)...
2017: PloS One
https://www.readbyqxmd.com/read/28275625/antibody-darts-on-target-for-acute-myelogenous-leukemia
#4
EDITORIAL
A John Barrett
No abstract text is available yet for this article.
February 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28270565/midostaurin-a-novel-protein-kinase-inhibitor-for-the-treatment-of-acute-myelogenous-leukemia-insights-from-human-absorption-metabolism-and-excretion-studies-of-a-bddcs-ii-drug
#5
Handan He, Phi Tran, Helen Gu, Vivienne Tedesco, Jin Zhang, Wen Lin, Ewa Gatlik, Kai Klein, Tycho Heimbach
The absorption, metabolism and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50 mg [14C]midostaurin dose, oral absorption was high (> 90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 h), CGP52421 (495 h), and CGP62221 (33...
March 7, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28231491/effect-of-granulocyte-colony-stimulating-factor-on-outcomes-in-patients-with-non-m3-acute-myelogenous-leukemia-treated-with-anthracycline-based-induction-7-3-regimen-chemotherapies
#6
Ka-Won Kang, Dae Sik Kim, Se Ryeon Lee, Hwa Jung Sung, Seok Jin Kim, Chul Won Choi, Byung Soo Kim, Yong Park
We analyzed the effects of granulocyte colony-stimulating factor (G-CSF) on outcomes in 315 anthracycline-based induction chemotherapy-treated patients with non-M3 acute myelogenous leukemia (AML). Patients were classified as follows: no G-CSF administration during induction (no G-CSF group; 112 patients); administration immediately upon neutropenia onset (absolute neutrophil counts (ANC)<1000/μL), but before febrile neutropenia (preemptive group; 74 patients); and administration following febrile neutropenia development (therapeutic group; 129 patients)...
February 8, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28229282/clinical-studies-in-hematologic-microtransplantation
#7
REVIEW
Kevin A David, Dennis Cooper, Roger Strair
The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy...
February 22, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#8
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n = 184), myelodysplastic syndrome (n = 69), acute lymphocytic leukemia (n = 57), chronic myelogenous leukemia (CML, n = 36), lymphoid neoplasms (n = 38), adult T cell leukemia/lymphoma (n = 18), and multiple myeloma (n = 12)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28185276/patient-age-and-number-of-apheresis-days-may-predict-development-of-secondary-myelodysplastic-syndrome-and-acute-myelogenous-leukemia-after-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-lymphoma
#9
Isabell Ge, Rima M Saliba, Farzaneh Maadani, Uday R Popat, Muzaffar H Qazilbash, Sai Ravi Pingali, Nina Shah, Sairah Ahmed, Qaiser Bashir, Yago Nieto, Richard E Champlin, Chitra Hosing
BACKGROUND: The goal of our study was to find predictors for the development of secondary myelodysplastic syndrome or acute myelogenous leukemia (s-MDS/AML) in patients with relapsed or refractory lymphoma who received high-dose chemotherapy and autologous stem cell transplantation (ASCT). STUDY DESIGN AND METHODS: We conducted a retrospective review of 295 patients with relapsed or refractory lymphoma who had undergone their first stem cell collection and ASCT...
February 10, 2017: Transfusion
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#10
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174131/application-of-vitamin-d-and-vitamin-d-analogs-in-acute-myelogenous-leukemia
#11
REVIEW
Huynh Cao, Yi Xu, Rosalia de Necochea-Campion, David J Baylink, Kimberly J Payne, Xiaolei Tang, Christina Ratanatharathorn, Yong Ji, Saied Mirshahidi, Chien-Shing Chen
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant, transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for AML requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients...
February 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28167452/tet2-exon-2-skipping-is-an-independent-favorable-prognostic-factor-for-cytogenetically-normal-acute-myelogenous-leukemia-aml-tet2-exon-2-skipping-in-aml
#12
Aminetou Mint Mohamed, Marie Balsat, Catherine Koering, Delphine Maucort-Boulch, Nicolas Boissel, Lea Payen-Gay, Meyling Cheok, Hussein Mortada, Didier Auboeuf, Christiane Pinatel, Mohamed El-Hamri, Isabelle Tigaud, Sandrine Hayette, Charles Dumontet, Emeline Cros, Pascale Flandrin-Gresta, Olivier Nibourel, Claude Preudhomme, Xavier Thomas, Franck-Emmanuel Nicolini, Françoise Solly, Denis Guyotat, Lydia Campos, Mauricette Michallet, Antony Ceraulo, Franck Mortreux, Eric Wattel
In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28161117/new-drugs-for-rare-diseases-in-children
#13
Klaus Rose
PURPOSE: United States (US) Pediatric Legislation (PL) was introduced in 1997 to improve children's health. The European Union PL (EUPL) has been in force since 2007. Both PLs facilitate additional pediatric research on primarily adult drugs. The EUPL declares that the forces of the market are not sufficient for children. Without a pediatric investigation plan, new drugs can no longer be registered with the European Union. New ways on how to facilitate drug development for rare pediatric diseases are being proposed...
February 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28157217/acute-myeloid-leukemia-targets-for-bispecific-antibodies
#14
REVIEW
S S Hoseini, N K Cheung
Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28156527/last-year-of-life-of-cancer-patients-who-are-adolescents-and-young-adults-aya-inpatient-patterns-and-disparities-in-a-population-based-study
#15
Elysia Marie Alvarez, Olga Saynina, Lee Sanders, Smita Bhatia, Lisa J Chamberlain
126 Background: Cancer is the leading cause of non-accidental death among adolescents and young adults (AYA) in the US. The last year of life involves significant inpatient resources for older patients. We sought to determine the quantity and pattern of inpatient care for AYA cancer decedents in the last year of life to learn their healthcare system impact and groups to target for intervention. METHODS: Using the California Office of Statewide Health Planning and Development private administrative database linked to death certificates, we performed a retrospective cross-sectional population-based analysis of patients aged 15-39 with cancer who died between 2000-2011...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28111465/differential-signaling-networks-of-bcr-abl-p210-and-p190-kinases-in-leukemia-cells-defined-by-functional-proteomics
#16
S Reckel, R Hamelin, S Georgeon, F Armand, Q Jolliet, D Chiappe, M Moniatte, O Hantschel
The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated...
February 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#17
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase have been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107581/mir-9-plays-a-role-in-il-10-mediated-expression-of-e-cadherin-in-acute-myelogenous-leukemia-cells
#18
Chie Nishioka, Takayuki Ikezoe, Bin Pan, Kailin Xu, Akihito Yokoyama
We previously showed that the CD82/STAT5/IL-10 axis is activated in CD34(+) /CD38(-) acute myelogenous leukemia (AML) cells which favor bone marrow microenvironment. The present study explored the novel biological function of IL-10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL-10 induced expression of E-cadherin, but not other adhesion molecules including VLA4, CD29, and LFA1. Downregulation of E-cadherin with a small interfering RNA (siRNA) suppressed the adhesion of leukemia cells to bone marrow-derived mesenchymal stem cells and enhanced the anti-leukemia effect of cytarabine (AraC)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28067901/targeting-samhd1-with-the-vpx-protein-to-improve-cytarabine-therapy-for-hematological-malignancies
#19
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#20
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
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