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Experimental Hematology

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https://www.readbyqxmd.com/read/27889516/lenalidomide-enhances-the-function-of-dendritic-cells-generated-from-patients-with-multiple-myeloma
#1
Manh-Cuong Vo, Truc Anh-NguyenThi, Hyun-Ju Lee, Thanh-Nhan Nguyen-Pham, Thangaraj Jaya Lakshmi, Sung-Hoon Jung, Hyeoung-Joon Kim, Je-Jung Lee
Lenalidomide (LEN) has been used as an immunomodulatory drug with direct and indirect anti-tumor effects. In this study, we evaluated the effect of LEN on the differentiation, maturation, and function of dendritic cells (DCs) in patients with multiple myeloma (MM) in vitro. Various doses of LEN were added after the monocytes had differentiated into immature DCs (imDCs) and activated into mature DCs (mDCs). LEN (5 μg/mL) was the optimal concentration to promote differentiation and maturation of DCs. imDCs treated with LEN showed enhanced endocytic capacity...
November 23, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in-b-progenitor-acute-lymphoblastic-leukemia
#2
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27865805/transcriptional-activation-by-mll-fusion-proteins-in-leukemogenesis
#3
REVIEW
Akihiko Yokoyama
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause aggressive leukemia. Fusion proteins of MLL and a component of the AF4 family/ENL family/P-TEFb complex (AEP) are responsible for two-thirds of MLL-associated leukemia cases. MLL-AEP fusion proteins trigger aberrant self-renewal of hematopoietic progenitors by constitutively activating self-renewal-related genes. MLL-AEP fusion proteins activate transcription initiation by loading the TATA-binding protein (TBP) to the TATA element via selectivity factor 1...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27864153/immunogenicity-of-murine-mpeg-red-blood-cells-and-the-risk-of-anti-peg-antibodies-in-human-blood-donors
#4
Yevgeniya Le, Wendy M Toyofuku, Mark D Scott
The immunocamouflage of non-ABO blood group antigens by membrane grafted mPEG may attenuate the risk of RBC alloimmunization. However, concerns have been raised as to the immunogenic risk of PEG and PEG-RBC. To assess these risks, murine and human studies were done. Mice were exposed to soluble PEG prior to, or between, multiple transfusions (∼60 day intervals) of control or mPEG-RBC and cell survival was determined by flow cytometry. In some studies, the control and mPEG-RBC groups were reversed following one or more transfusions...
November 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27856324/mll-af4-binds-directly-to-a-bcl-2-specific-enhancer-and-modulates-h3k27-acetylation
#5
Laura Godfrey, Jon Kerry, Ross Thorne, Emmanouela Repapi, James O J Davies, Marta Tapia, Erica Ballabio, Jim R Hughes, Huimin Geng, Marina Konopleva, Thomas A Milne
Survival rates for children and adults carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in ALL is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we demonstrated that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. Here, we perform a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
November 14, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27833035/tumor-necrosis-factor-%C3%AE-in-the-onset-and-progression-of-leukemia
#6
REVIEW
Xiaoxi Zhou, Zhuoya Li, Jianfeng Zhou
Tumor necrosis factor alpha (TNF-α), originally described as an anti-neoplastic cytokine, has been found, in apparent contradiction to its name, to play an important role in promoting the development and progression of malignant disease. Targeting TNF-α with TNF antagonists has elicited an objective response in certain solid tumors in phase I and II clinical trials. This review focuses on the relationship of TNF-α expressed by leukemia cells and adverse clinical features of leukemia. TNF-α is involved in all steps of leukemogenesis, including cellular transformation, proliferation, angiogenesis, and extramedullary infiltration...
November 8, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27833034/mysm1-expression-in-the-bone-marrow-niche-is-not-essential-for-hematopoietic-maintenance
#7
Jessica C Petrov, Anastasia Nijnik
Myb-Like SWIRM and MPN domains 1 (MYSM1) is a chromatin-binding protein, essential for hematopoietic stem cell (HSC) maintenance and differentiation in humans and mouse models. HSCs in mammalian bone marrow exist in close interactions with many non-hematopoietic cell types in their microenvironment, collectively known as the bone marrow niche. While cell-intrinsic activities of MYSM1 within the hematopoietic cells are known to play an important role in hematopoietic homeostasis, Mysm1 expression is also widely observed in non-hematopoietic cells, and MYSM1 is implicated as an important regulator of mesenchymal stem cell (MSC) differentiation, osteoblast function, and adipogenesis within the bone marrow...
November 7, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27826124/-off-the-shelf-immunotherapy-with-ipsc-derived-rejuvenated-cytotoxic-t-lymphocytes
#8
Miki Ando, Hiromitsu Nakauchi
Adoptive T cell therapy to target and kill tumor cells shows promise and induces durable remissions in selected malignancies. However, for most cancers, clinical utility is limited. Cytotoxic T lymphocytes (CTLs) continuously exposed to viral or tumor antigens, with long-term expansion, may become unable to proliferate ("exhausted"). To exploit fully rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific CTLs is a potentially powerful approach. We review recent progress in engineering iPSC-derived T cells and prospects for clinical translation...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27826123/novel-strategies-of-adoptive-immunotherapy-how-natural-killer-cells-may-change-the-treatment-of-elderly-patients-with-acute-myeloblastic-leukemia
#9
REVIEW
Roberto M Lemoli, Sarah Parisi, Antonio Curti
Although many attempts have been made to identify novel molecular-targeted therapies for patients with acute myeloid leukemia, their translation into the clinic have had limited impact. In particular, the question of effective and curative treatments for elderly patients, who are not eligible for stem cell transplantation, remains an unmet medical need. To answer this question, a wide range of immunologic therapeutic strategies, mostly T cell based, have been proposed and investigated. At present, however, the clinical results have been largely unsatisfactory...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27826122/variable-aldehyde-dehydrogenase-activity-and-effects-on-chemosensitivity-of-primitive-human-leukemic-cells
#10
A Bogen, C Buske, W Hiddemann, S K Bohlander, O Christ
Aldehyde dehydrogenase (ALDH) activity is an established feature of primitive normal human hematopoietic cells in which it has been associated with a high expression of the 1A1 isoform of ALDH. High ALDH1A1 activity has been reported to also characterize cells that propagate malignant populations arising in other tissues, but the regulation and basis of ALDH activity in primary human leukemic cells has not been well studied. We obtained samples from patients with newly diagnosed AML (n=21) and CML (n=8) and analyzed different phenotypically and functionally defined subsets for their ALDH activity using the ALDEFLUOR(®) kit and expression of the ALDH1A1 gene...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27821246/erratum-to-effect-of-roflumilast-novel-phosphodiesterase-4-inhibitor-on-lung-chronic-graft-versus-host-disease-in-mice
#11
Sei Won Kim, Ji Young Lim, Chin Kook Rhee, Ji Hye Kim, Chan Kwon Park, Tae Jung Kim, Chul Soo Cho, Chang Ki Min, Hyoung Kyu Yoon
No abstract text is available yet for this article.
November 4, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27821245/erratum-to-autophagy-regulates-the-cell-cycle-of-mouse-hspcs-in%C3%A2-a%C3%A2-nutrient-dependent-manner
#12
Yan Cao, Aihong Zhang, Jinyang Cai, Na Yuan, Weiwei Lin, Shengbing Liu, Fei Xu, Lin Song, Xin Li, Yixuan Fang, Zhen Wang, Zhijian Wang, Jian Wang, Han Zhang, Wenli Zhao, Shaoyan Hu, Suping Zhang, Jianrong Wang
No abstract text is available yet for this article.
November 4, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27789332/granulocyte-colony-stimulating-factor-receptor-signaling-in-severe-congenital-neutropenia-chronic-neutrophilic-leukemia-and-related-malignancies
#13
REVIEW
Pankaj Dwivedi, Kenneth D Greis
Granulocyte colony-stimulating factor is a hematopoietic cytokine that stimulates neutrophil production and hematopoietic stem cell mobilization by initiating the dimerization of homodimeric granulocyte colony-stimulating factor receptor. Different mutations of CSF3R have been linked to a unique spectrum of myeloid disorders and related malignancies. Myeloid disorders caused by the CSF3R mutations include severe congenital neutropenia, chronic neutrophilic leukemia, and atypical chronic myeloid leukemia. In this review, we provide an analysis of granulocyte colony-stimulating factor receptor, various mutations, and their roles in the severe congenital neutropenia, chronic neutrophilic leukemia, and malignant transformation, as well as the clinical implications and some perspective on approaches that could expand our knowledge with respect to the normal signaling mechanisms and those associated with mutations in the receptor...
October 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27773671/moz-and-bmi1-act-synergistically-to-maintain-hematopoietic-stem-cells
#14
Bilal N Sheikh, Donald Metcalf, Anne K Voss, Tim Thomas
Chromatin plays a central role in maintaining hematopoietic stem cells and during their stepwise differentiation. Although a large number of histone modifications and chromatin-modifying enzymes have been identified, how these act in concert to produce specific phenotypic outcomes remains to be established. MOZ (KAT6A) is a lysine acetyltransferase and enhances transcription at target gene loci. In contrast, the Polycomb group protein BMI1 (PCGF4) is part of the transcriptionally repressive PRC1 complex. Despite their opposing effects on transcription, MOZ and BMI1 regulate biological systems in a similar manner...
October 24, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27765615/everolimus-restrains-the-il-17a-dependent-osteoclast-like-transdifferentiation-of-dendritic-cells-in-multiple-myeloma
#15
Marco Tucci, Stefania Stucci, Anna Passarelli, Stella D'Oronzo, Franco Silvestris
Interleukin-17A (IL-17A) promotes the osteoclast (OC)-like differentiation of dendritic cells (DCs) in multiple myeloma (MM) and contributes to the pathogenesis of myeloma bone disease (MBD). In our study, everolimus (EVR) abrogated the in vitro OC-like activity of DCs from 12 MM patients significantly. Exploring the EVR effects, we found that the inhibition of the osteoerosive activity of OC-DCs was mostly due to the blockade of signals driven by the IL-17A receptor toward the CCAAT/enhancer-binding protein beta/musculoaponeurotic fibrosarcoma oncogene homolog B axis Therefore, MM patients with MBD would probably benefit from mammalian target of rapamycin inhibition...
October 17, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27765614/genetically-re-engineered-k562%C3%A2-cells-significantly-expand-and-functionally-activate-cord-blood-natural-killer-cells-potential-for-adoptive-cellular-immunotherapy
#16
Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V Baxi, William Quish, Carmella van de Ven, Mitchell S Cairo
Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562)...
October 17, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27751872/csk-binding-protein-controls-red-blood-cell-development-via-regulation-of-lyn-tyrosine-kinase-activity
#17
Janice H C Plani-Lam, Neli S Slavova-Azmanova, Nicole Kucera, Alison Louw, Jiulia Satiaputra, Peter Singer, Kong-Peng Lam, Margaret L Hibbs, Evan Ingley
Erythropoiesis is controlled principally through erythropoietin (Epo) receptor signaling, which involves Janus kinase 2 (JAK2) and Lyn tyrosine kinase, both of which are important for regulating red blood cell (RBC) development. Negative regulation of Lyn involves C-Src kinase (Csk)-mediated phosphorylation of its C-terminal tyrosine, which is facilitated by the transmembrane adaptor Csk-binding protein (Cbp). Although Cbp has significant functions in controlling Lyn levels and activity in erythroid cells in vitro, its importance to primary erythroid cell development and signaling has remained unclear...
October 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27751871/hif1%C3%AE-induced-pdgfr%C3%AE-signaling-promotes-developmental-hsc-production-via-il-6-activation
#18
Sung-Eun Lim, Virginie Esain, Wanda Kwan, Lindsay N Theodore, Mauricio Cortes, Isaura M Frost, Sarah Y Liu, Trista E North
Hematopoietic stem cells (HSCs) have the ability to both self-renew and differentiate into all of the mature blood cell lineages and thereby reconstitute the entire blood system. Therefore, HSCs are therapeutically valuable for treatment of hematological malignances and bone marrow failure. We showed recently that transient glucose elevation elicited dose-dependent effects on HSCs through elevated metabolic activity and subsequent reactive oxygen species-mediated induction of Hypoxia-Inducible Factor 1α (Hif1α)...
October 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27725192/aml1-eto-promotes-sirt1-expression-to-enhance-leukemogenesis-of-t-8-21-acute-myeloid-leukemia
#19
Lei Zhou, Qian Wang, Xiaosu Chen, Lin Fu, Xiaodong Zhang, Lijun Wang, Ailing Deng, Dandan Li, Jing Liu, Na Lv, Lili Wang, Yonghui Li, Daihong Liu, Li Yu, Liping Dou
Recently, SIRT1 was found to play an important role in a variety of solid and hematologic malignancies. The expression and function of SIRT1 may differ completely depending on cell type and gene subtype, and it can act as a tumor suppressor or oncogene. We describe how SIRT1 mRNA and protein levels are overexpressed in t(8;21) AML cells. AML1-ETO triggers the activation of SIRT1 by binding at AML1 binding sites on the SIRT1 promoter. Pharmacologic targeting or RNAi-mediated inhibition of SIRT1 induces G1 arrest, apoptosis, and proliferation inhibition that is more sensitive in AML1-ETO-positive than AML1-ETO-negative cell lines...
October 8, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27720937/using-zebrafish-models-of-leukemia-to-streamline-drug-screening-and-discovery
#20
Adam P Deveau, Victoria L Bentley, Jason N Berman
Current treatment strategies for acute leukemias largely rely on nonspecific cytotoxic drugs that result in high therapy-related morbidity and mortality. Cost effective, pertinent animal models are needed to link in vitro studies with the development of new therapeutic agents in clinical trials on a high-throughput scale. However, targeted therapies have had limited success moving from bench-to-clinic, often due to unexpected off-target effects. The zebrafish has emerged as a reliable in vivo tool for modeling human leukemia...
October 6, 2016: Experimental Hematology
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