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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
#1
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/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#2
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
#3
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/27908728/activation-of-evi1-transcription-by-the-lef1-%C3%AE-catenin-complex-with-p53-alteration-in-myeloid-blast-crisis-of-chronic-myeloid-leukemia
#4
Nawin Manachai, Yusuke Saito, Shingo Nakahata, Avinash Govind Bahirvani, Tomomi Osato, Kazuhiro Morishita
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blastic crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#5
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27906795/factors-determining-the-outcome-of-hematopoietic-stem-cell-transplantation-in-patients-with-acute-lymphoblastic-leukemia-at-king-faisal-specialist-hospital-and-research-center-riyadh-saudi-arabia
#6
Suleimman Al-Sweedan, Amal Al-Seraihy, Ali Al-Ahmari, Abdullah Al-Jefri, Viqaruddin Mohammed, Rafat Jafri, Khawar Siddiqui, Mouhab Ayas
Medical records of 82 patients with acute lymphoblastic leukemia (ALL) who underwent hematopoietic cell transplantation (HCT) at our institution from 2005 to 2011 were reviewed. Forty-five patients were male (54.8%). The median age at HCT was 7.46 years (range, 0.98 to 14.31 y), the median time to HCT after diagnosis was 12.56 months. Ten patients were below the age of 1 year (12%). All patients were in complete remission at the time of HCT. In 83 transplants, 64 patients received HCT from human leukocyte antigen-identical-related donors and 19 from other donors...
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
#7
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/27905839/gene-therapy-to-cure-hiv-where-to-from-here
#8
Rowena Johnston
A variety of approaches are being tested to cure HIV, but with the exception of the Berlin patient case, none has been successful. The Berlin patient, positive for both HIV and acute myeloid leukemia (AML), received two stem cell transplants from a donor homozygous for the CCR5delta32 mutation. In the 8 years since his second transplant, he has remained free of both HIV and AML. This case provides strong proof-of-principle that a cure for HIV is possible and might be achieved through gene therapy. Several technological barriers must be resolved and are discussed here, including the safe delivery of the intervention throughout the body of the infected person, increased efficiency of gene editing, and avoidance of resistance to the therapy...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27904889/reactive-oxygen-species-in-bcr-abl1-expressing-cells-relevance-to-chronic-myeloid-leukemia
#9
Joanna Antoszewska-Smith, Elzbieta Pawlowska, Janusz Blasiak
Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis...
December 1, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27904139/interphase-fluorescence-in-situ-hybridization-ifish-in-untreated-al-amyloidosis-has-an-independent-prognostic-impact-by-abnormality-type-and-treatment-category
#10
E Muchtar, A Dispenzieri, S K Kumar, R P Ketterling, D Dingli, M Q Lacy, F K Buadi, S R Hayman, P Kapoor, N Leung, R Chakraborty, W Gonsalves, R Warsame, T V Kourelis, S Russell, J A Lust, Y Lin, R S Go, S Zeldenrust, R A Kyle, S V Rajkumar, M A Gertz
The significance of interphase fluorescence in-situ hybridization (iFISH) by regimen type was assessed in 692 AL amyloidosis patients with iFISH at diagnosis. First line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52 vs 77%; P=0...
December 1, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27903646/whole-transcriptome-sequencing-identified-a-distinct-subtype-of-acute-lymphoblastic-leukemia-with-predominant-genomic-abnormalities-of-ep300-and-crebbp
#11
Maoxiang Qian, Hui Zhang, Shirley Kow-Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Charnise Goodings, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Zhenhua Li, Thuan Chong Quah, Hany Ariffin, Ah Moy Tan, Shuhong Shen, Deepa Bhojwani, Shaoyan Hu, Suning Chen, Huyong Zheng, Ching-Hon Pui, Allen Eng-Juh Yeoh, Jun J Yang
Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54...
November 30, 2016: Genome Research
https://www.readbyqxmd.com/read/27902595/prognostic-impact-of-viral-reactivations-in-acute-myeloid-leukemia-patients-undergoing-allogeneic-stem-cell-transplantation-in-first-complete-response
#12
Sarah Guenounou, Cécile Borel, Emilie Bérard, Edwige Yon, Marylise Fort, Catherine Mengelle, Sarah Bertoli, Audrey Sarry, Suzanne Tavitian, Françoise Huguet, Michel Attal, Christian Récher, Anne Huynh
Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#13
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901031/effect-of-body-mass-index-on-overall-survival-of-patients-with-allogeneic-hematopoietic-stem-cell-transplantation
#14
J Yang, S-L Xue, X Zhang, Y-N Zhou, L-Q Qin, Y-P Shen, D-P Wu
BACKGROUND/OBJECTIVES: The present work was performed to investigate the association between body mass index (BMI) before transplantation and the overall survival (OS) of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS/METHODS: Data from 310 adults who were diagnosed with acute leukemia and underwent allo-HSCT between March 2001 and December 2011 were analyzed. According to the suggested BMI categories for Asian population, patients with BMIs of ⩾23 and ⩾25 kg/m(2) were identified as overweight and obese, respectively...
November 30, 2016: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27899806/preleukemia-one-name-many-meanings
#15
REVIEW
H P Koeffler, G Leong
Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia which nearly always progress to AML. More recently investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations which were also present at diagnosis of AML...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899803/novel-targets-in-the-treatment-of-chronic-graft-versus-host-disease
#16
REVIEW
A Im, F T Hakim, S Z Pavletic
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved agents in GVHD underscore the importance of developing novel therapies...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899802/genomic-and-transcriptional-landscape-of-p2ry8-crlf2-positive-childhood-acute-lymphoblastic-leukemia
#17
C Vesely, C Frech, C Eckert, G Cario, A Mecklenbräuker, U Zur Stadt, K Nebral, F Kraler, S Fischer, A Attarbaschi, M Schuster, C Bock, H Cavé, A von Stackelberg, M Schrappe, M A Horstmann, G Mann, O A Haas, R Panzer-Grümayer
Children with P2RY8-CRLF2-positive ALL have an increased relapse risk. Their mutational and transcriptional landscape as well as the respective patterns at relapse remains largely elusive. We therefore performed an integrated analysis of whole-exome and RNA-sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway activating mutations in 76% of cases at diagnosis and virtually all relapses...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899775/-leukemia
#18
Minenori Eguchi-Ishimae, Mariko Eguchi
Leukemia is derived from hematopoietic stem/progenitor cells that have acquired genetic abnormalities, leading to malignant transformation. The basis of therapyfor leukemia is a combination of anti-cancer drugs based on risk stratification. The overall 5-year survival rate in leukemia patients of all ages is still 40%, although it has improved in pediatric patients. Leuke- mia itself is a heterogeneous disease that includes various entities/subtypes with different pathogenic gene aberrations. Selection of the treatment strategylargelydepends on risk stratification, and this in turn is mainlybased on specific recurrent chromosome aberrations...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27899359/how-i-treat-atypical-chronic-myeloid-leukemia
#19
Jason Gotlib
Atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML) is a rare myelodysplastic syndrome/myeloproliferative neoplasm for which no current standard of care exists. The challenges of atypical CML relate to its heterogeneous clinical and genetic features, high rate of transformation to acute myeloid leukemia, and historically poor survival. Therefore, allogeneic hematopoietic stem cell transplantation should always be an initial consideration for eligible patients with a suitable donor. Non-transplant approaches for treating aCML have otherwise largely relied on adopting treatment strategies used for MDS and MPN...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#20
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
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