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Leukemia stem cell

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https://www.readbyqxmd.com/read/29232178/rapid-decrease-in-krt14-and-tp53-mrna-expression-in-the-buccal-mucosa-of-patients-receiving-total-body-irradiation-for-allogeneic-stem-cell-transplantation
#1
J Chmara, J W L Browning, H Atkins, M Sabloff, B C McKay
The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis...
December 12, 2017: Radiation Research
https://www.readbyqxmd.com/read/29231051/midostaurin-in-combination-with-standard-chemotherapy-for-treatment-of-newly-diagnosed-fms-like-tyrosine-kinase-3-flt3-mutation-positive-acute-myeloid-leukemia
#2
Miryoung Kim, Sherry Williams
OBJECTIVE: To evaluate the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation in newly diagnosed FLT3-mutated acute myeloid leukemia (AML). DATA SOURCE: A literature search of PubMed and MEDLINE (September 2017) was performed using the terms midostaurin, PKC412, FLT3 gene, and acute myeloid leukemia. STUDY SELECTION/DATA EXTRACTION: Clinical trials evaluating the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation were reviewed for the treatment of newly diagnosed FLT3-mutated AML...
December 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29230958/treatment-related-mortality-in-relapsed-childhood-acute-lymphoblastic-leukemia
#3
Trausti Oskarsson, Stefan Söderhäll, Johan Arvidson, Erik Forestier, Thomas Leth Frandsen, Marit Hellebostad, Päivi Lähteenmäki, Ólafur G Jónsson, Ida Hed Myrberg, Mats Heyman
BACKGROUND: Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment-related toxicity impacts survival. PROCEDURE: In this retrospective population-based study, we described the causes of death and estimated the risk for treatment-related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL-92 and ALL-2000 trials...
December 12, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29230125/older-patients-with-acute-myeloid-leukemia-treatment-challenges-and-future-directions
#4
REVIEW
Laura Finn, Andrew Dalovisio, James Foran
Background: Even though acute myeloid leukemia (AML) occurs most commonly in adults ≥60 years, the treatment of AML in older patients remains a significant challenge. Methods: We reviewed the current literature regarding patient assessment tools, treatment options, and current therapies in clinical trial for patients with AML who are ≥60 years. Results: Our approach to the older patient with AML is evolving with better understanding of the unique disease epidemiology in this population and the development of tools to assess individual patient functional status, including grading systems for comorbidities, geriatric assessment tools, and measurements of frailty...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29228587/chronic-myeloid-leukemia-progenitor-cells-require-autophagy-when-leaving-hypoxia-induced-quiescence
#5
Angela Ianniciello, Pierre-Yves Dumas, Claire Drullion, Amélie Guitart, Arnaud Villacreces, Yan Peytour, Jean Chevaleyre, Philippe Brunet de la Grange, Isabelle Vigon, Vanessa Desplat, Muriel Priault, Persio Dello Sbarba, Zoran Ivanovic, François-Xavier Mahon, Jean-Max Pasquet
Albeit tyrosine kinase inhibitors anti-Abl used in Chronic Myeloid Leukemia (CML) block the deregulated activity of the Bcr-Abl tyrosine kinase and induce remission in 90% of patients, they do not eradicate immature hematopoietic compartments of leukemic stem cells. To elucidate if autophagy is important for stem cell survival and/or proliferation, we used culture in low oxygen concentration (0.1% O2 for 7 days) followed back by non-restricted O2 supply (normoxic culture) to mimic stem cell proliferation and commitment...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226717/atypical-chronic-myeloid-leukemia-a-rare-entity-with-management-challenges
#6
Prajwal Dhakal, Krishna Gundabolu, Catalina Amador, Supratik Rayamajhi, Vijaya Raj Bhatt
The aim of our study was to review the clinicopathologic features and management of atypical chronic myeloid leukemia (aCML). Relevant manuscripts published in English were searched using PubMed. aCML is diagnosed as per WHO 2016 classification in the presence of leukocytosis ≥13 × 109/l with circulating neutrophil precursors ≥10%, monocytes less than 10%, minimal basophils, hypercellular bone marrow with granulocytic proliferation and dysplasia, bone marrow blast less than 20% and absence of BCR/ABL fusion gene...
December 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29226497/similar-outcome-of-allogeneic-stem-cell-transplantation-after-myeloablative-and-sequential-conditioning-regimen-in-patients-with-refractory-or-relapsed-acute-myeloid-leukemia-a-study-from-the-soci%C3%A3-t%C3%A3-francophone-de-greffe-de-moelle-et-de-th%C3%A3-rapie-cellulaire
#7
Justine Decroocq, Raphaël Itzykson, Stéphane Vigouroux, Mauricette Michallet, Ibrahim Yakoub-Agha, Anne Huynh, Florence Beckerich, Felipe Suarez, Patrice Chevallier, Stéphanie Nguyen-Quoc, Marie-Pierre Ledoux, Laurence Clement, Yosr Hicheri, Gaëlle Guillerm, Jérôme Cornillon, Nathalie Contentin, Martin Carre, Natacha Maillard, Mélanie Mercier, Mohamad Mohty, Yves Beguin, Jean-Henri Bourhis, Amandine Charbonnier, Charles Dauriac, Jacques-Olivier Bay, Didier Blaise, Eric Deconinck, Charlotte Jubert, Nicole Raus, Regis Peffault de Latour, Nathalie Dhedin
Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%)...
December 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29223442/exosomes-derived-from-imatinib-resistant-chronic-myeloid-leukemia-cells-mediate-a-horizontal-transfer-of-drug-resistant-trait-by-delivering-mir-365
#8
Qing-Hua Min, Xiao-Zhong Wang, Jing Zhang, Qing-Gen Chen, Shu-Qi Li, Xiao-Qing Liu, Jing Li, Jing Liu, Wei-Ming Yang, Yu-Huan Jiang, Yan-Mei Xu, Jin Lin, Qiu-Fang Gao, Fan Sun, Lei Zhang, Bo Huang
Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR...
December 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29222245/novel-approaches-to-therapy-in-cml
#9
REVIEW
Ravi Bhatia
Treatment with tyrosine kinase inhibitors (TKIs) results in remission and prolongation of survival in most chronic myeloid leukemia (CML) patients but fails to eliminate the leukemia stem cells (LSCs) responsible for disease development and propagation. This accounts for the clinical observation that TKI discontinuation leads to rapid leukemia relapse. Most patients require continued treatment to prevent relapse, with associated risk of relapse, toxicity, teratogenic effects, financial burden, and noncompliance...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222241/inherited-bone-marrow-failure-syndromes-considerations-pre-and-posttransplant
#10
REVIEW
Blanche P Alter
Patients with inherited bone marrow failure syndromes are usually identified when they develop hematologic complications such as severe bone marrow failure, myelodysplastic syndrome, or acute myeloid leukemia. They often have specific birth defects or other physical abnormalities that suggest a syndrome, and sequencing of specific genes or next-generation sequencing can determine or confirm the particular syndrome. The 4 most frequent syndromes are Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222233/current-management-of-philadelphia-chromosome-positive-all-and-the-role-of-stem-cell-transplantation
#11
REVIEW
Farhad Ravandi
Treatment of Philadelphia chromosome positive acute lymphoblastic leukemia exemplifies how the addition of potent targeted agents, directed at the molecular aberrations responsible for leukemic transformation, can overcome resistance mechanisms to traditional regimens and lead to improved outcomes. The introduction of BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) has significantly improved the outcomes not only by allowing more patients to undergo allogeneic hematopoietic cell transplantation (alloHCT) but also by decreasing our reliance on this potentially toxic strategy, particularly in the less fit population...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222232/minimal-residual-disease-in-adult-all-technical-aspects-and-implications-for-correct-clinical-interpretation
#12
REVIEW
Monika Brüggemann, Michaela Kotrova
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222114/blood-vitronectin-is-a-major-activator-of-lif-and-il-6-in-the-brain-through-integrin-fak-and-upar-signaling
#13
M P Keasey, C Jia, L F Pimentel, R S Sante, C Lovins, T Hagg
We defined how blood-derived vitronectin (VTN) rapidly and potently activates leukemia inhibitory factor (LIF) and pro-inflammatory interleukin 6 (IL-6) in vitro and after vascular injury in the brain. VTN (not fibrinogen, fibronectin, laminin-111, collagen-I) robustly increased LIF and IL-6 within 4 hr in C6-astroglioma cells, while VTN-/- mouse plasma was less effective than wildtype. LIF and IL-6 were induced by intracerebral injection of rhVTN in mice, but less by intracerebral hemorrhage in VTN-/- than wildtype littermates...
December 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29221109/protein-phosphatase-4-regulatory-subunit-2-ppp4r2-is-recurrently-deleted-in-acute-myeloid-leukemia-and-required-for-efficient-dna-double-strand-break-repair
#14
Julia K Herzig, Lars Bullinger, Alpaslan Tasdogan, Philipp Zimmermann, Martin Schlegel, Veronica Teleanu, Daniela Weber, Frank G Rücker, Peter Paschka, Anna Dolnik, Edith Schneider, Florian Kuchenbauer, Florian H Heidel, Christian Buske, Hartmut Döhner, Konstanze Döhner, Verena I Gaidzik
We have previously identified a recurrent deletion at chromosomal band 3p14.1-p13 in patients with acute myeloid leukemia (AML). Among eight protein-coding genes, this microdeletion affects the protein phosphatase 4 regulatory subunit 2 (PPP4R2), which plays an important role in DNA damage response (DDR). Investigation of mRNA expression during murine myelopoiesis determined that Ppp4r2 is higher expressed in more primitive hematopoietic cells. PPP4R2 expression in primary AML samples compared to healthy bone marrow was significantly lower, particularly in patients with 3p microdeletion or complex karyotype...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215199/neurotrophically-induced-mesenchymal-progenitor-cells-derived-from-induced-pluripotent-stem-cells-enhance-neuritogenesis-via-neurotrophin-and-cytokine-production
#15
Rachel M Brick, Aaron X Sun, Rocky S Tuan
Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs...
December 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#16
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29214689/distinct-factors-determine-the-kinetics-of-disease-relapse-in-adults-transplanted-for-acute-myeloid-leukaemia
#17
C Craddock, J Versluis, M Labopin, G Socie, A Huynh, E Deconinck, L Volin, N Milpied, J H Bourhis, A Rambaldi, P Chevallier, D Blaise, M Manz, E Vellenga, M-C Vekemans, J Maertens, J Passweg, P Vyas, C Schmid, B Löwenberg, G Ossenkoppele, M Mohty, J J Cornelissen, A Nagler
Disease recurrence remains the major cause of death in adults with acute myeloid leukemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized...
December 7, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29212977/-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-complicated-by-concomitant-achromobacter-xylosoxidans-and-corynebacterium-striatum-bacteremia-following-allogeneic-hematopoietic-stem-cell-transplantation
#18
Yuta Katayama, Kouhei Kyo, Koji Iwato, Takeshi Okatani, Ryota Imanaka, Mitsuhiro Itagaki, Shinya Katsutani, Hideki Asaoku
A 54-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) underwent hematopoietic stem cell transplantation from an HLA-matched sibling. Subsequently, she suffered from chronic graft versus host disease (GvHD) and received medical treatment. Fever developed on day 697 and resulted in a shock state at 10 h after the visit. Achromobacter xylosoxidans was detected in the initial blood culture on day 699. General conditions exacerbated even after the start of meropenem hydrate (MEPM, Meropen®) administration, with Corynebacterium striatum detected as an additional species in the initial blood culture on day 701...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212976/-congenital-leukemia-showing-lineage-switch-following-induction-chemotherapy-and-attaining-long-term-remission-after-hla-haploidentical-stem-cell-transplantation
#19
Kazuki Furudate, Yuri Okimoto, Kumiko Ando, Yuichi Taneyama, Hidemasa Ochiai, Harumi Kakuda
Congenital leukemia is a rare subgroup of childhood leukemia. Lineage switches in leukemic cells are relatively rare events, which have been occasionally reported in congenital leukemia. To the best of our knowledge, the survival of congenital leukemia patients with lineage switch has not been previously documented. This lack of documentation may be attributable to extremely poor prognosis of these patients. We describe a case of a newborn female with initial diagnosis of MLL-AF4 positive B-precursor acute lymphoblastic leukemia, who developed lineage switch to acute monocytic leukemia following the induction therapy...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212799/lif-activated-jak-signaling-determines-esrrb-expression-during-late-stage-reprogramming
#20
Delun Huang, Ling Wang, Jingyue Duan, Chang Huang, Xiuchun Cindy Tian, Ming Zhang, Young Tang
The regulatory process of naïve-state induced pluripotent stem cells (iPSCs) generation is not well understood. Leukemia inhibitory factor (LIF) activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb) serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs). However, the inter-connection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear...
December 6, 2017: Biology Open
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