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Leukemic stem cell

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https://www.readbyqxmd.com/read/28218044/leukemia-microvesicles-affect-healthy-hematopoietic-stem-cells
#1
Farnaz Razmkhah, Masoud Soleimani, Davood Mehrabani, Mohammad Hossein Karimi, Sedigheh Amini Kafi-Abad, Mani Ramzi, Mahdiyar Iravani Saadi, Javad Kakoui
Microvesicles are released by different cell types and shuttle mRNAs and microRNAs which have the possibility to transfer genetic information to a target cell and alter its function. Acute myeloid leukemia is a malignant disorder, and leukemic cells occupy all the bone marrow microenvironment. In this study, we investigate the effect of leukemia microvesicles on healthy umbilical cord blood hematopoietic stem cells to find evidence of cell information transferring. Leukemia microvesicles were isolated from acute myeloid leukemia patients and were co-incubated with healthy hematopoietic stem cells...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#2
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28216566/phenotypic-and-functional-alterations-of-hematopoietic-stem-and-progenitor-cells-in-an-in-vitro-leukemia-induced-microenvironment
#3
Jean-Paul Vernot, Ximena Bonilla, Viviana Rodriguez-Pardo, Natalia-Del Pilar Vanegas
An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC) with the REH acute lymphocytic leukemia (ALL) cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (HSPC, CD34+ cells). We showed that the normal homeostatic control exerted by the MSC over the HSPC is considerably lost in this leukemic microenvironment: HSPC increased their proliferation rate and adhesion to MSC...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28215704/cpg-island-hypermethylation-mediated-by-dnmt3a-is-a-consequence-of-aml-progression
#4
David H Spencer, David A Russler-Germain, Shamika Ketkar, Nichole M Helton, Tamara L Lamprecht, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Marwan Shinawi, Peter Westervelt, Jacqueline E Payton, Lukas D Wartman, John S Welch, Richard K Wilson, Matthew J Walter, Daniel C Link, John F DiPersio, Timothy J Ley
DNMT3A mutations occur in ∼25% of acute myeloid leukemia (AML) patients. The most common mutation, DNMT3A(R882H), has dominant negative activity that reduces DNA methylation activity by ∼80% in vitro. To understand the contribution of DNMT3A-dependent methylation to leukemogenesis, we performed whole-genome bisulfite sequencing of primary leukemic and non-leukemic cells in patients with or without DNMT3A(R882) mutations. Non-leukemic hematopoietic cells with DNMT3A(R882H) displayed focal methylation loss, suggesting that hypomethylation antedates AML...
February 13, 2017: Cell
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#5
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28210257/kinetics-of-cytotoxic-lymphocytes-reconstitution-after-induction-chemotherapy-in-elderly-aml-patients-reveals-progressive-recovery-of-normal-phenotypic-and-functional-features-in-nk-cells
#6
Jérôme Rey, Cyril Fauriat, Eloïse Kochbati, Florence Orlanducci, Aude Charbonnier, Evelyne D'Incan, Pascale Andre, François Romagne, Bernadette Barbarat, Norbert Vey, Daniel Olive
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202504/expression-profiling-of-circulating-microvesicles-reveals-intercellular-transmission-of-oncogenic-pathways
#7
Gloria Milani, Tobia Lana, Silvia Bresolin, Sanja Aveic, Anna Pasto, Chiara Frasson, Geertruy Te Kronnie
: Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information under normal or pathological condition. MVs released by cancer cells may incorporate diverse biomolecules (e.g. active lipids, proteins and RNA) which can be delivered and internalized by recipient cells, potentially altering gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate MVs as vehicles of protein-coding messages...
February 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28202494/fumarate-hydratase-is-a-critical-metabolic-regulator-of-hematopoietic-stem-cell-functions
#8
Amelie V Guitart, Theano I Panagopoulou, Arnaud Villacreces, Milica Vukovic, Catarina Sepulveda, Lewis Allen, Roderick N Carter, Louie N van de Lagemaat, Marcos Morgan, Peter Giles, Zuzanna Sas, Marta Vila Gonzalez, Hannah Lawson, Jasmin Paris, Joy Edwards-Hicks, Katrin Schaak, Chithra Subramani, Deniz Gezer, Alejandro Armesilla-Diaz, Jimi Wills, Aaron Easterbrook, David Coman, Chi Wai Eric So, Donal O'Carroll, Douglas Vernimmen, Neil P Rodrigues, Patrick J Pollard, Nicholas M Morton, Andrew Finch, Kamil R Kranc
Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure...
February 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28197208/molecular-mutations-and-their-cooccurrences-in-cytogenetically-normal-acute-myeloid-leukemia
#9
REVIEW
Mengning Wang, Chuanwei Yang, Le Zhang, Dale G Schaar
Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#10
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28190861/acute-undifferentiated-leukemia-stem-cell-acute-leukemia-showing-differentiation-to-langerhans-cell-like-cells-in-lymph-nodes
#11
Takanori Fukuta, Shu Nakamoto, Yoshinori Hashimoto, Takayuki Tanaka, Yusuke Tokuyasu, Junko Maruyama, Hiromi Omura, Norihiko Hino, Satoshi Kuwamoto, Ichiro Murakami
A 75-year-old woman was referred to our hospital with suspected leukemia. Complete blood count demonstrated WBC 3,810/µl with 26% blasts, Hb of 11.7 g/dl and Plt of 18.0×10(4)/µl. Bone marrow aspiration revealed blasts (86.3%) with expressions of CD34, CD7, TdT, CD33, and CD117. MPO was negative. Chromosomal analysis of the bone marrow showed isolated trisomy 10 in all leukemic cells (20/20). Swelling of superficial lymph nodes was also observed. Cervical lymph node biopsy revealed leukemic blasts which had the same phenotype as those in the bone marrow except that proliferation of Langerhans cell-like cells (LCs) was observed in the paracortex...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28183848/long-term-observation-reveals-high-frequency-engraftment-of-human-acute-myeloid-leukemia-in-immunodeficient-mice
#12
Anna M Paczulla, Stephan Dirnhofer, Martina Konantz, Michael Medinger, Helmut R Salih, Kathrin Rothfelder, Dimitrios A Tsakiris, Jakob R Passweg, Pontus Lundberg, Claudia Lengerke
Repopulation of immunodeficient mice remains the primary method to func-tionally assess human acute myeloid leukemia. Published data report en-graftment of ~40-66% of cases, mostly belonging to intermediate or poor risk subtypes. Here we report that extending follow-up beyond the standard analysis end-points of 10 to 16 weeks post-transplantation permitted leukemic engraftment from nearly every xenotransplanted acute myeloid leukemia case (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune phenotypes and genetic signatures when compared to corresponding pre-transplant cells, and were furthermore able to induce leukemia in re-transplantation assays...
February 9, 2017: Haematologica
https://www.readbyqxmd.com/read/28178710/diagnosis-and-management-of-leukemic-and-lymphomatous-meningitis
#13
REVIEW
Hemant Murthy, Claudio Anasetti, Ernesto Ayala
BACKGROUND: Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia. METHODS: The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of leukemic and lymphomatous meningitis. RESULTS: Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28176227/neoplasms-in-the-bone-marrow-niches-disturbance-of-the-microecosystem
#14
REVIEW
Li-Li Mu, Fang Ke, Xiao-Lin Guo, Jie-Jing Cai, Deng-Li Hong
Increasing studies have revealed that the interaction between malignant cells and the microenvironment (so called niche) in the bone marrow can influence the development and progression of the hematopoietic malignancies. Here, we reviewed the current findings in the field, focusing the niche alterations in promoting the emergency of malignancies, in interfering with the blood reconstitution of normal hematopoietic stem and progenitor cells, and in protecting leukemic stem cells from therapy which causes disease relapse...
February 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28176225/regulation-of-normal-and-leukemic-stem-cells-through-cytokine-signaling-and-the-microenvironment
#15
REVIEW
Virginia Camacho, Victoria McClearn, Sweta Patel, Robert S Welner
Leukemias depend on transformed stem cells for their growth and thus these cells represent important therapeutic targets. However, leukemic stem cells resemble normal hematopoietic stem cells (HSCs) with respect to most surface markers, gene expression patterns, and ability to be transplanted. Furthermore, the microenvironment that supports healthy HSCs non-hematopoietic populations, and immune cells correspondingly, the cytokines, adhesion molecules and signal transduction pathways are also impaired during leukemogenesis...
February 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28169005/nelarabine-associated-reversible-guillain-barr%C3%A3-like-syndrome-or-myelopathy-in-an-adult-patient-with-primary-refractory-t-lymphoblastic-lymphoma
#16
Chrysavgi Lalayanni, Eirini Baldoumi, Sotiris Papayiannopoulos, Konstantia Tziola, Riad Saloum, Achilles Anagnostopoulos
Nelarabine is a purine analogue used for the treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma mainly as a bridge to stem cell transplantation. The water-soluble prodrug of 9-beta-D-arabinofuranosyl guanine (Ara-G) is phosphorylated within leukemic cells to form ara-G triphosphate (ara-GTP), which terminates DNA chain elongation, resulting in cell death. The drug received accelerated approval by the US Food and Drug Administration (FDA) on October 2005 based on the induction of complete remissions in 2 phase II trials...
November 17, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28161479/canthin-6-one-induces-cell-death-cell-cycle-arrest-and-differentiation-in-human-myeloid-leukemia-cells
#17
Heron F Vieira Torquato, Antonio C Ribeiro-Filho, Marcus V Buri, Roberto T Araújo Júnior, Renata Pimenta, José Salvador R de Oliveira, Valdir C Filho, Antonio Macho, Edgar J Paredes-Gamero, Domingos T de Oliveira Martins
BACKGROUND: Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. METHODS: Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin(+)) and leukemia stem cell population (CD34(+)CD38(-)Lin(-/low))...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28159739/introduction-to-the-review-series-on-leukemic-stem-cells
#18
Bob Lowenberg
No abstract text is available yet for this article.
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#19
Hind Medyouf
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies such as myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of HSCs, including self-renewal, quiescence, differentiation and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28137304/understanding-of-leukemic-stem-cells-and-their-clinical-implications
#20
REVIEW
Xuefei Wang, Shile Huang, Ji-Long Chen
Since leukemic stem cells (LSCs) or cancer stem cells (CSCs) were found in acute myeloid leukemia (AML) in 1997, extensive studies have been contributed to identification and characterization of such cell populations in various tissues. LSCs are now generally recognized as a heterogeneous cell population that possesses the capacities of self-renewal, proliferation and differentiation. It has been shown that LSCs are regulated by critical surface antigens, microenvironment, intrinsic signaling pathways, and novel molecules such as some ncRNAs...
January 30, 2017: Molecular Cancer
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