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The BAF45a/PHF10 Subunit of SWI/SNF-like Chromatin Remodeling Complexes is Essential for Hematopoietic Stem Cell MaintenanceOpen in a New Window

The ability of hemopoietic stem cells to self-renew and differentiate into downstream lineages is dependent on specialized chromatin environments that establish and maintain stage-specific patterns of gene expression. However, the epigenetic factors responsible for mediating these regulatory events remain poorly defined. Here we provide evidence that BAF45a/PHF10, a subunit of SWI/SNF-like chromatin remodeling complexes, is essential for adult hemopoietic stem cell (HSC) maintenance and myeloid lineage development. (Veneta Krasteva, Gerald R. Crabtree, Julie A. Lessard) - 2016-12-05

 

From the Bedside to the Bench: New Discoveries on Blood Cell Fate and FunctionOpen in a New Window

two words that exemplified this year’s ISEH meeting. Leaders in the field of hematology from around the world gathered in San Diego in August 2016 to discuss cutting edge research on diverse topics, such as hemoglobin switching, HSC emergence, leukemogenesis, and aging. Major questions discussed included the “when, where, and how” of hematopoietic emergence, bone marrow residence, and disease origination. This meeting summary covers some of the conference highlights. (Eirini Trompouki, Eugenia Flores-Figueroa, Daniel Lucas, Teresa Bowman) - 2016-12-05

 

Impairment of fetal hematopoietic stem cell function in the absence ofOpen in a New Window

Fanconi Anemia (FA), results from mutations in genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests hematopoietic defects originate in utero which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. (Sakiko Suzuki, Ronny R. Racine, Nathan A. Manalo, Sharon B. Cantor, Glen D. Raffel) - 2016-11-30

 

Lenalidomide enhances the function of dendritic cells generated from patients with multiple myelomaOpen in a New Window

Lenalidomide enhanced the function of dendritic cells generated from patients with multiple myeloma by stimulating the capacity of allogeneic T cells, inhibiting the generation of immunosuppressive cells, altering naïve T cells toward Th1 polarization, and generating potent myeloma-specific cytotoxic T lymphocytes for multiple myeloma treatment. (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) - 2016-11-23

 

Ikaros: exploiting and targeting the hematopoietic stem cell niche in B-progenitor acute lymphoblastic leukemiaOpen in a New Window

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. (Michelle L. Churchman, Charles G. Mullighan) - 2016-11-16

 

Transcriptional activation by MLL fusion proteins in leukemogenesisOpen in a New Window

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. (Akihiko Yokoyama) - 2016-11-16

 

Immunogenicity of Murine mPEG-Red Blood Cells and the Risk of Anti-PEG Antibodies in Human Blood DonorsOpen in a New Window

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. (Yevgeniya Le, Wendy M. Toyofuku, Mark D. Scott) - 2016-11-15

 

MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylationOpen in a New Window

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. (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) - 2016-11-14

 

expression in the bone marrow niche is not essential for hematopoietic maintenanceOpen in a New Window

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. (Jessica C. Petrov, Anastasia Nijnik) - 2016-11-08

 

Tumor necrosis factor α in the onset and progression of leukemiaOpen in a New Window

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. (Xiaoxi Zhou, Zhuoya Li, Jianfeng Zhou) - 2016-11-08

 

Variable aldehyde dehydrogenase activity and effects on chemosensitivity of primitive human leukemic cellsOpen in a New Window

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 cmlA1 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 acute myeloid leukemia (AML; n = 21) and chronic myeloid leukemia (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. (A. Bogen, C. Buske, W. Hiddemann, S.K. Bohlander, O. Christ) - 2016-11-05

 

“Off-the-shelf” Immunotherapy with iPSC-Derived Rejuvenated Cytotoxic T LymphocytesOpen in a New Window

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. (Miki Ando, Hiromitsu Nakauchi) - 2016-11-05

 

Novel strategies of adoptive immunotherapy: How natural killer cells may change the treatment of elderly patients with acute myeloblastic leukemiaOpen in a New Window

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. (Roberto M. Lemoli, Sarah Parisi, Antonio Curti) - 2016-11-05

 

Erratum to “Effect of roflumilast, novel phosphodiesterase-4 inhibitor, on lung chronic graft-versus-host disease in mice”Open in a New Window

This article contains two corresponding authors. However, the authors regret that Chang Ki Min was missed as a corresponding author in the original publication. Chang Ki Min and Hyoung Kyu Yoon contributed equally to the original article as a corresponding author. The authors would like to apologize for any inconvenience caused. (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) - 2016-11-04

 

Erratum to “Autophagy regulates the cell cycle of mouse HSPCs in a nutrient-dependent manner”Open in a New Window

The authors regret that they found a misuse of the western blotting result in the Fig 1A (Cao et al., Experimental Hematology 43 (2015):229–242), which is actually the result for mouse bone marrow cells, not for mouse bone marrow Lin− cells. They have reperformed the experiment with isolated bone marrow Lin− cells from mice. Although the western blotting band pattern and conclusion are the same between the bone marrow cells and bone marrow Lin− cells, They requested to replace the existing Fig 1A. (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) - 2016-11-04

 

Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignanciesOpen in a New Window

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. (Pankaj Dwivedi, Kenneth D. Greis) - 2016-10-24

 

MOZ and BMI1 act synergistically to maintain hematopoietic stem cellsOpen in a New Window

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. (Bilal N. Sheikh, Donald Metcalf, Anne K. Voss, Tim Thomas) - 2016-10-20

 

Everolimus restrains the IL-17A-dependent osteoclast-like transdifferentiation of dendritic cells in multiple myelomaOpen in a New Window

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. (Marco Tucci, Stefania Stucci, Anna Passarelli, Stella D'Oronzo, Franco Silvestris) - 2016-10-17

 

Genetically re-engineered K562 cells significantly expand and functionally activate cord blood natural killer cells: Potential for adoptive cellular immunotherapyOpen in a New Window

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). (Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V. Baxi, William Quish, Carmella van de Ven, Mitchell S. Cairo) - 2016-10-17

 

HIF1α-induced PDGFRβ signaling promotes developmental HSC production via IL-6 activationOpen in a New Window

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). (Sung-Eun Lim, Virginie Esain, Wanda Kwan, Lindsay N. Theodore, Mauricio Cortes, Isaura M. Frost, Sarah Y. Liu, Trista E. North) - 2016-10-14

 

Csk-binding protein controls red blood cell development via regulation of Lyn tyrosine kinase activityOpen in a New Window

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. (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) - 2016-10-14

 

AML1–ETO promotes SIRT1 expression to enhance leukemogenesis of t(8;21) acute myeloid leukemiaOpen in a New Window

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. (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) - 2016-10-07

 

Using zebrafish models of leukemia to streamline drug screening and discoveryOpen in a New Window

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. (Adam P. Deveau, Victoria L. Bentley, Jason N. Berman) - 2016-10-06

 

MiR-17-92 represses PTPROt and PP2A phosphatases and amplifies tonic BCR signaling in DLBCL cellsOpen in a New Window

B-cell receptor (BCR) signaling plays a pivotal role in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and targeting the BCR pathway is a highly promising therapeutic strategy in this malignancy. The oncogenic microRNA miR-17-92 modulates multiple cellular processes such as survival, proliferation, apoptosis, angiogenesis, and BCR signaling. In the present study, we identified new targets of miR-17-92, PTPROt (protein phosphatase, receptor type O, truncated) and PP2A (protein phosphatase 2A) phosphatases, which regulate the activity of spleen tyrosine kinase (SYK) and AKT, critical components of BCR signal transduction in DLBCL cells. (Ewa Jablonska, Patryk Gorniak, Maciej Szydlowski, Tomasz Sewastianik, Emilia Bialopiotrowicz, Anna Polak, Krzysztof Warzocha, Przemyslaw Juszczynski) - 2016-10-06

 

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukemia clonesOpen in a New Window

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonally derived mature CD5high B cells; however, the cellular origin of CLL is still unknown. Patients with CLL also harbor variable numbers of CD5low B cells, but the clonal relationship of these cells to the bulk disease is unknown and can have important implications for monitoring, treating, and understanding the biology of CLL. Here, we use B-cell receptors (BCRs) as molecular barcodes to first show by single-cell BCR sequencing that the great majority of CD5low B cells in the blood of CLL patients are clonally related to CD5high CLL B cells. (Rachael J.M. Bashford-Rogers, Anne L. Palser, Clare Hodkinson, Joanna Baxter, George A. Follows, George S. Vassiliou, Paul Kellam) - 2016-09-27

 

Alterations in the bone marrow microenvironment may elicit defective hematopoiesis: a comparison of aplastic anemia, chronic myeloid leukemia, and normal bone marrowOpen in a New Window

Hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. The specific causes and mechanisms underlying dysregulated hematopoiesis are unknown. Here, BM biopsy specimens from patients with aplastic anemia (AA) and chronic myeloid leukemia (CML) and normal marrow were analyzed by semiquantitative immunohistochemistry to determine changes in the hematopoietic stem cell (HSC) compartment and BM microenvironment. HSC levels were lowest in AA and highest in CML. (Meerim Park, Chan-Jeoung Park, Young Wook Cho, Seongsoo Jang, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Young Ho Lee) - 2016-09-27

 

Clinical-grade regulatory T cells: Comparative analysis of large-scale expansion conditionsOpen in a New Window

Recent clinical trials have indicated the high potential of regulatory T cells (Tregs) in the prevention of acute and chronic graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation, but immune interventions require large numbers of Tregs. With respect to their limited natural occurrence, development and optimization of protocols for large-scale expansion of clinical-grade Tregs are essential if considered for therapeutic use. We compared different clinical-grade large-scale expansion protocols for repetitive transfer of large numbers of Tregs in clinical trials for the prevention of acute and/or chronic GvHD. (Sarvari Velaga, Christina Alter, Ulrike Dringenberg, Christina T. Thiesler, Sandra Kuhs, Sven Olek, Sya N. Ukena, Anke Franzke) - 2016-09-27

 

Proinflammatory signals are insufficient to drive definitive hematopoietic specification of human HSCs in vitroOpen in a New Window

Recent studies in zebrafish and mice have revealed that proinflammatory signaling is a positive regulator of definitive hematopoietic development. Whether proinflammatory signaling also regulates human hematopoietic specification remains unknown. Here, we explored the impact of the proinflammatory cytokines tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), and interleukin-1β (IL1β) on in vitro hematopoietic differentiation using human pluripotent stem cells. Gene expression analysis and enzyme-linked immunosorbent assay revealed the absence of a proinflammatory signature during hematopoietic development of human pluripotent stem cells. (Alessandra Giorgetti, Julio Castaño, Clara Bueno, Rafael Díaz de la Guardia, Mario Delgado, Anna Bigas, Lluis Espinosa, Pablo Menendez) - 2016-09-27

 

AC220 and AraC cause differential inhibitory dynamics in patient-derived M5-AML with FLT3-ITD and, thus, ultimately distinct therapeutic outcomesOpen in a New Window

Engrafting the bone marrow cells of a patient with M5 acute myeloid leukemia into immunocompromised mice (AM7577) resulted in serially transferrable stable AML and eventual mortality. The disease starts in the bone marrow and then expands to peripheral areas, which is typical of M5 leukemogenesis, where high leukemic burden in blood is coincident with symptoms/mortality. The leukemic cells in the mice had myeloid morphology, phenotypes, and genotypes (including the internal tandem duplication of FMS-like tyrosine kinase receptor 3 gene [FLT3-ITD]) similar to those of the original patient. (Xiaoyu An, Jinping Liu, Na Wang, Di Wang, Liang Huang, Likun Zhang, Jie Cai, Jean-Pierre Wery, Demin Zhou, Jianfeng Zhou, Qi-Xiang Li) - 2016-09-23

 

The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrityOpen in a New Window

Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. (Emma L. Cambridge, Zoe McIntyre, Simon Clare, Mark J. Arends, David Goulding, Christopher Isherwood, Susana S. Caetano, Carmen Ballesteros Reviriego, Agnieszka Swiatkowska, Leanne Kane, Katherine Harcourt, The Sanger Mouse Genetics Project, David J. Adams, Jacqueline K. White, Anneliese O. Speak) - 2016-09-22

 

Constitutive Kit activity triggers B-cell acute lymphoblastic leukemia-like disease in miceOpen in a New Window

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and, in most cases, is of pro- or pre-B cell origin (B-ALL). The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of-function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B-lineage origin. (Robin R. Weidemann, Rayk Behrendt, Kristina B. Schoedel, Werner Müller, Axel Roers, Alexander Gerbaulet) - 2016-09-21

 

Pharmacological inhibition of AKT activity in human CD34 cells enhances their ability to engraft immunodeficient miceOpen in a New Window

Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplantation remains limited by the inability to expand functional HSCs ex vivo. To determine the role of phosphoinositide 3-kinase (PI3K)/AKT signaling in human hematopoietic stem and progenitor cell (HSPC) maintenance, we examined the effect of genetic and pharmacological inhibition of AKT on human umbilical cord blood (UCB) CD34+ cells. We found that knock-down of AKT1 in human UCB CD34+ cells using short interfering RNAs targeting AKT1 enhances their quiescence and colony formation potential in vitro. (Sisi Chen, Rui Gao, Michihiro Kobayashi, Hao Yu, Chonghua Yao, Reuben Kapur, Mervin C. Yoder, Yan Liu) - 2016-09-16

 

Sustained enhancement of OCTN1 transporter expression in association with hydroxyurea induced γ-globin expression in erythroid progenitorsOpen in a New Window

The clinical benefits of hydroxyurea (HU) treatment in patients with sickle cell disease (SCD) are due largely to increased γ-globin expression. However, mechanisms that control γ-globin expression by HU in erythroid progenitors are incompletely understood. Here, we investigated the role of two HU transporters, urea transporter B (UTB) and organic cation/carnitine transporter 1 (OCTN1), in this process. Endogenous expression of both transporters peaked toward the end of erythroid differentiation. (Aisha L. Walker, Solomon F. Ofori-Acquah) - 2016-09-08

 

TEMPORARY REMOVAL: Assessment of hematopoietic and neurologic pathophysiology of -associated protein X-1 deficiency in a -knockout mouse modelOpen in a New Window

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. (Emanuele G. Coci, Nadine Thau-Habermann, Tobias Maetzig, Zhixiong Li, Christoph Klein, Susanne Petri, Axel Schambach) - 2014-10-28
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