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Leukemia stem cells

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https://www.readbyqxmd.com/read/28447034/the-biomarkers-of-leukemia-stem-cells-in-acute-myeloid-leukemia
#1
REVIEW
Yahui Ding, Huier Gao, Quan Zhang
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by morphology and chromosome aberrations with high mortality. Leukemia stem cells (LSCs) in AML played important roles in leukemia initiation, progression, and were considered to be the root of chemotherapeutic drug resistance and disease relapse. The identification and targeting LSCs depended on membrane markers like CD34, CD38, CD123, TIM3, CD25, CD32 and CD96. In addition, the transcription factors were also therapeutic targets in eradicating LSCs, such as histone deacetylases (HDACs), NF-κB, HIF-1α and β-catenin...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446316/-prognostic-value-of-recurrent-molecular-genetics-and-epigenetics-abnormity-in-t-lymphoblastic-lymphoma-leukemia-review
#2
Wei Guan, Yu Jing, Li Yu
T lymphoblastic lymphoma / leukemia is a strong invasive and has a high incidence of various molecular genetic abnormalities. The NOTCH1 / FBXW7 mutation is one of the most common mutations, and related with good prognosis in T-LBL / ALL. PTEN mutation, a poor prognostic factor, could be overcome by NOTCH1 mutations in pediatric patients to some extent. Patients with MLL gene abnormality and loss of heterozygosity 6q have worse prognosis than those with normal karyotype. The incidence of MLL gene abnormality, RUNX1 mutation and DNMT3A mutation in early precursor T-lymphoblastic leukemia was higher than that of other mature subtypes, which could be used as risk stratification factors...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446272/-efficacy-comparison-of-different-salvage-treatment-regimens-for-patients-with-refractory-relapsed-acute-myeloid-leukemia
#3
Wen-Hui Gao, Hong-Min Li, Jing-Yi Yu, Ya-Li Zheng, Li-Hua Wu, Qing-Guo Liu, Jun-Fan Li, Chun-Hua Liu, Yi-Ming Hu, Ning Xu, Shang-Zhu Li, Ying-Chang Mi, Ping-Ping Huang
OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28445872/successful-management-of-decitabine-prior-to-full-dose-idarubicin-and-cytarabine-in-the-treatment-of-refractory-recurrent-acute-myeloid-leukemia
#4
Hongyu Zhao, Li Xu, Yongjian Yang, Jianhua Shao, Ping Chen, Xuebin Dong, Linping Gu, Daqi Li
AIMS: To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). METHODS: We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. RESULTS: After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9...
April 27, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28441794/reciprocal-interactions-of-leukemic-cells-with-bone-marrow-stromal-cells-promote-enrichment-of-leukemic-stell-cell-compartments-in-response-to-curcumin-and-daunorubicin
#5
Saeed Mohammadi, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Fariba Rad, Bahram Chahardouli, Javid Sabour Takanlu, Shahrbano Rostami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
A predominant challenge in developing curative leukemia therapy is interactions of leukemic cells with the bone marrow stromal microenvironment. We aimed to investigate the role of stromal cells, such as bone marrow mesenchymal stromal cells (BMSCs) and osteoblasts (OBs), in curcumin (CUR) and daunorubicin (DNR) induced apoptosis of acute myeloid leukemia (AML) cells. We used KG1 and U937 as leukemia cell line models and treated them with CUR and DNR. The cells were then co-cultured with BMSCs or a combination of BMSCs and OBs as feeders...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28439910/abo-incompatibility-in-mismatched-unrelated-donor-allogeneic-hematopoietic-cell-transplantation-for-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-ebmt
#6
Jonathan Canaani, Bipin N Savani, Myriam Labopin, Mauricette Michallet, Charles Craddock, Gerard Socié, Lisa Volin, Johan A Maertens, Charles Crawley, Didier Blaise, Per T Ljungman, Jan Cornelissen, Nigel Russell, Frédéric Baron, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs...
April 25, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28439109/efficacy-and-safety-of-carfilzomib-regimens-in-multiple-myeloma-patients-relapsing-after-autologous-stem-cell-transplant-aspire-and-endeavor-outcomes
#7
P Hari, M-V Mateos, R Abonour, S Knop, W Bensinger, H Ludwig, K Song, R Hajek, P Moreau, D S Siegel, S Feng, M Obreja, S K Aggarwal, K Iskander, H Goldschmidt
Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib-lenalidomide-dexamethasone; ENDEAVOR, carfilzomib-dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide-dexamethasone; ENDEAVOR, bortezomib-dexamethasone)...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28439106/lenalidomide-adriamycin-dexamethasone-rad-for-induction-followed-by-stem-cell-transplant-in-newly-diagnosed-myeloma
#8
S Knop, C Langer, M Engelhardt, L-O Mügge, A Reichle, W Rösler, F Bassermann, B Hertenstein, A Kunitz, C Röllig, H Ostermann, K Schäfer-Eckart, M Ringhoffer, A Günther, C Junghanss, H Biersack, M Schreder, A Liebert, S Held, H Einsele, R C Bargou
Leukemia accepted article preview online, 25 April 2017. doi:10.1038/leu.2017.124.
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28438857/reduced-competitive-repopulation-capacity-of-multipotential-hematopoietic-stem-cells-in-the-bone-marrow-of-friend-virus-infected-fv2-resistant-mice
#9
Michael W Epperly, Xichen Zhang, Renee Fisher, Wen Hou, Darcy Franicola, Donna Shields, Michael Quickel, Pamela Hankey-Giblin, Hong Wang, Joel S Greenberger
BACKGROUND/AIM: The polycythemia form of Friend leukemia virus (FVP) causes splenomegaly and lethal erythroleukemia in Fv-2(s)-susceptible mouse strains. We sought to determine whether the hematopoietic stem cell (HSC) pool was expanded in Fv-2(r)-resistant mice. MATERIALS AND METHODS: The 120-day bone marrow transplantation competitive repopulation assay was used to determine whether FVP-infected Fv-2(r) C57BL/6 mice demonstrated expansion of the HSC pool compared to the pool of committed hematopoietic progenitor cells in the same marrow assayed in vitro...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#10
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28436588/reduced-erg-dosage-impairs-survival-of-hematopoietic-stem-and-progenitor-cells
#11
Ying Xie, Mia Lee Koch, Xin Zhang, Melanie J Hamblen, Frank J Godinho, Yuko Fujiwara, Huafeng Xie, Jan-Henning Klusmann, Stuart H Orkin, Zhe Li
ERG, an ETS family transcription factor frequently overexpressed in human leukemia, has been implicated as a key regulator of hematopoietic stem cells. However, how ERG controls normal hematopoiesis, particularly at the stem and progenitor cell level, and how it contributes to leukemogenesis remain incompletely understood. Using homologous recombination, we generated an Erg knockdown allele (Erg(kd) ) in which Erg expression can be conditionally restored by Cre recombinase. Erg(kd/kd) animals die at E10.5-E11...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28433882/hypothyroidism-following-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-myeloid-leukemia
#12
Michael Medinger, Deborah Zeiter, Dominik Heim, Jörg Halter, Sabine Gerull, André Tichelli, Jakob Passweg, Nicole Nigro
BACKGROUND: Hypothyroidism may complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT); we therefore analyzed risk factors in this study. PATIENTS AND METHODS: We studied 229 patients with acute myeloid leukemia (AML) who underwent an allo-HSCT between 2003 and 2013 with different conditioning regimens (myeloablative, reduced-intensity, chemotherapy-based, or total body irradiation-based). Thyroid-stimulating hormone (TSH) and free thyroxine levels (fT4) were available in 104 patients before and after allo-HSCT...
April 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28432223/fli1-level-during-megakaryopoiesis-affects-thrombopoiesis-and-platelet-biology
#13
Karen K Vo, Danuta J Jarocha, Randolph B Lyde, Vincent Hayes, Christopher S Thom, Spencer K Sullivan, Deborah L French, Mortimer Poncz
Friend Leukemia Virus Integration 1 (FLI1), a critical transcription factor (TF) during megakaryocyte differentiation, is amongst genes hemizygously deleted in Jacobsen syndrome, resulting in a macrothrombocytopenia termed Paris-Trousseau syndrome (PTSx). Recently, heterozygote human FLI1 mutations have been ascribed to cause thrombocytopenia. We studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand these clinical disorders, beginning with iPSCs generated from a PTSx patient and iPSCs from a control line with a targeted heterozygous FLI1 knockout (FLI1(+/-))...
April 21, 2017: Blood
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#14
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423730/the-sclttaxbcr-abl-transgenic-mouse-model-closely-reflects-the-differential-effects-of-dasatinib-on-normal-and-malignant-hematopoiesis-in-chronic-phase-cml-patients
#15
Claudia Schubert, Nicolas Chatain, Till Braunschweig, Mirle Schemionek, Kristina Feldberg, Melanie Hoffmann, Olli Dufva, Satu Mustjoki, Tim H Brümmendorf, Steffen Koschmieder
The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was shown to impact on normal hematopoiesis and cells of the immune system.Due to the fact that the murine in vivo studies so far have not been performed in a chronic-phase CML model under steady-state conditions, our aim was to study the hematopoietic effects of dasatinib (20 mg/kg p.o...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423578/endothelial-microparticles-delivering-microrna-155-into-t-lymphocytes-are-involved-in-the-initiation-of-acute-graft-versus-host-disease-following-allogeneic-hematopoietic-stem-cell-transplantation
#16
Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng, Qiuling Wu, Linghui Xia
Endothelial microparticles (EMPs) upregulation has been observed in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and significantly higher than the levels in plasma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416638/eya2-a-target-activated-by-plzf-is-critical-for-plzf-rara-induced-leukemogenesis
#17
Ryoichi Ono, Masahiro Masuya, Satomi Ishii, Naoyuki Katayama, Tetsuya Nosaka
PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28416471/chemotherapy-resistant-human-acute-myeloid-leukemia-cells-are-not-enriched-for-leukemic-stem-cells-but-require-oxidative-metabolism
#18
Thomas Farge, Estelle Saland, Fabienne de Toni, Nesrine Aroua, Moshen Hosseini, Robin Perry, Claudie Bosc, Mayumi Sugita, Lucille Stuani, Marine Fraisse, Sarah Scotland, Clément Larrue, Héléna Boutzen, Virginie Féliu, Marie-Laure Nicolau-Travers, Stephanie Cassant-Sourdy, Nicolas Broin, Marion David, Nizar Serhan, Audrey Sarry, Suzanne Tavitian, Tony Kaoma, Laurent Vallar, Jason Iacovoni, Laetitia K Linares, Camille Montersino, Remy Castellano, Emmanuel Griessinger, Yves Collette, Olivier Duchamp, Yara Barreira, Pierre Hirsch, Tony Palama, Lara Gales, Francois Delhommeau, Barbara H Garmy-Susini, Jean-Charles Portais, Francois Vergez, Mary Selak, Gwenn Danet-Desnoyers, Martin Carroll, Christian Récher, Jean Emmanuel Sarry
Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSCs). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenograft (PDX) with cytarabine. Cytarabine residual AML cells are enriched neither in immature, quiescent cells nor LSCs. Strikingly, cytarabine-resistant pre-existing and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status...
April 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28415763/low-numbers-of-pre-leukemic-fusion-genes-are-frequently-present-in-umbilical-cord-blood-without-affecting-dna-damage-response
#19
Pavol Kosik, Milan Skorvaga, Matus Durdik, Lukas Jakl, Ekaterina Nikitina, Eva Markova, Katarina Kozics, Eva Horvathova, Igor Belyaev
Despite widely accepted notion that many childhood leukemias are likely developed from hematopoietic stem/progenitor cells (HSPC) with pre-leukemic fusion genes (PFG) formed in embryonic/fetal development, the data on PFG incidence in newborns are contradictive. To provide a better understanding of a prenatal origin of leukemia, umbilical cord blood from 500 newborns was screened for the presence of the most frequent PFG associated with pediatric B-cell acute lymphoblastic leukemia. This screening revealed relatively high incidence of ETV6-RUNX1, BCR-ABL1 (p190) and MLL-AF4 at very low frequencies, averaging ~14 copies per 100,000 cells...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415626/hematopoietic-stem-progenitor-cells-are-less-prone-to-undergo-apoptosis-than-lymphocytes-despite-similar-dna-damage-response
#20
Matus Durdik, Pavol Kosik, Jana Kruzliakova, Lukas Jakl, Eva Markova, Igor Belyaev
Hematopoietic stem/progenitor CD34+ cells (HSPC) give rise to all types of blood cells and represent a key cellular target for origination of leukemia. Apoptosis and repair of DNA double strand breaks (DSB) are vital processes in leukemogenesis. High doses of ionizing radiation are the best known agent that induces leukemia, but less is known about the leukemogenic potential of low doses. While umbilical cord blood (UCB) serves as a valuable source of the HSPC for both research and clinics, the data on DNA damage response and apoptosis in UCB HSPC are very limited...
March 22, 2017: Oncotarget
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