Abstract：
:Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcriptome RNA sequencing, splice-isoform-specific quantitative RT-PCR (qRT-PCR), nanoproteomics, stromal coculture, and BC LSC xenotransplantation analyses. Cumulatively, these studies show that the alternative splicing of multiple prosurvival BCL2 family genes promotes malignant transformation of myeloid progenitors into BC LSCS that are quiescent in the marrow niche and that contribute to therapeutic resistance. Notably, sabutoclax, a pan-BCL2 inhibitor, renders marrow-niche-resident BC LSCs sensitive to TKIs at doses that spare normal progenitors. These findings underscore the importance of alternative BCL2 family splice-isoform expression in BC LSC maintenance and suggest that the combinatorial inhibition of prosurvival BCL2 family proteins and BCR-ABL may eliminate dormant LSCs and obviate resistance.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Goff DJ,Court Recart A,Sadarangani A,Chun HJ,Barrett CL,Krajewska M,Leu H,Low-Marchelli J,Ma W,Shih AY,Wei J,Zhai D,Geron I,Pu M,Bao L,Chuang R,Balaian L,Gotlib J,Minden M,Martinelli G,Rusert J,Dao KH,Shazanddoi
10.1016/j.stem.2012.12.011subject
Has Abstractpub_date
2013-03-07 00:00:00pages
316-28issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(12)00716-3journal_volume
12pub_type
杂志文章相关文献
Cell Stem Cell文献大全abstract：:Aging is characterized by a decrease in genome integrity, impaired organ maintenance, and an increased risk of cancer, which coincide with clonal dominance of expanded mutant stem and progenitor cell populations in aging tissues, such as the intestinal epithelium, the hematopoietic system, and the male germline. Here ...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2015.05.002
更新日期：2015-06-04 00:00:00
abstract：:To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clo...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.03.002
更新日期：2012-05-04 00:00:00
abstract：:Pluripotent stem cells are defined by their capacity to differentiate into all three tissue layers that comprise the body. Chimera formation, generated by stem cell transplantation to the embryo, is a stringent assessment of stem cell pluripotency. However, the ability of human pluripotent stem cells (hPSCs) to form e...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.11.017
更新日期：2016-01-07 00:00:00
abstract：:In a study of young adults chosen as unrelated hematopoietic stem cell donors for patients with hematological malignancies, leukemia-associated mutations were detectable in cells from 44% of donors. Donor-origin mutant clones engrafted in recipients and expanded during the first 100 days after transplant, but donor-de...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2020.01.022
更新日期：2020-03-05 00:00:00
abstract：:The generation of induced pluripotent stem cells (iPSCs) provides a novel method to facilitate investigations into the mechanisms that control stem cell pluripotency and self-renewal. Myc has previously been shown to be critical for murine embryonic stem cell (mESC) maintenance, while also enhancing directed reprogram...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2010.06.023
更新日期：2010-09-03 00:00:00
abstract：:Similarities between basal cell carcinoma (BCC) tumor cells and hair follicle keratinocytes had previously suggested that BCC originates within the hair follicle bulge stem cell niche. However, in the current Nature Cell Biology, Youssef et al. (2010) show that BCC instead originates in the interfollicular epidermis. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2010.03.009
更新日期：2010-04-02 00:00:00
abstract：:Fanconi anemia (FA) is an inherited DNA repair disorder characterized by progressive bone marrow failure (BMF) from hematopoietic stem and progenitor cell (HSPC) attrition. A greater understanding of the pathogenesis of BMF could improve the therapeutic options for FA patients. Using a genome-wide shRNA screen in huma...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.03.002
更新日期：2016-05-05 00:00:00
abstract：:Tumors contain hostile inflammatory signals generated by aberrant proliferation, necrosis, and hypoxia. These signals are sensed and acted upon acutely by the Toll-like receptors (TLRs) to halt proliferation and activate an immune response. Despite the presence of TLR ligands within the microenvironment, tumors progre...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.12.001
更新日期：2017-04-06 00:00:00
abstract：:In homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here, we examine th...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2009.06.004
更新日期：2009-09-04 00:00:00
abstract：:Since the inception of nuclear reprogramming, the parallels between this process and tumorigenesis have become increasingly apparent. Recent studies by Abad et al. and Ohnishi et al. have now formalized this connection by demonstrating that the same transcription factors used for reprogramming to pluripotency drive tu...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2014.02.003
更新日期：2014-03-06 00:00:00
abstract：:Achieving immune tolerance through cell transplantation is a promising approach for treating autoimmune disease. In this issue of Cell Stem Cell, Akiyama et al. (2012) demonstrate that human and mouse mesenchymal stem cells can induce immune suppression by attracting and killing autoreactive T cells, which stimulates ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2012.04.013
更新日期：2012-05-04 00:00:00
abstract：:In this issue of Cell Stem Cell, Wang et al. (2014) describe a signaling axis present in bone marrow stromal cells that suppresses inflammation and myeloid expansions. Loss of endothelial Notch signaling leads to deregulation of miR-155 expression, activation of NF-kB, and increased proinflammatory cytokine production...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2014.06.010
更新日期：2014-07-03 00:00:00
abstract：:Cellular metabolism plays important functions in dictating stem cell behaviors, although its role in stomach epithelial homeostasis has not been evaluated in depth. Here, we show that the energy sensor AMP kinase (AMPK) governs gastric epithelial progenitor differentiation. Administering the AMPK activator metformin d...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2020.03.006
更新日期：2020-06-04 00:00:00
abstract：:Trophoblast stem cells (TSCs) arise from the first cell fate decision in the developing embryo and generate extra-embryonic lineages, giving rise to the fetal portion of the placenta. Mouse embryonic and extra-embryonic lineages are strictly separated by a distinct epigenetic barrier, which is not fully overcome follo...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.08.005
更新日期：2015-11-05 00:00:00
abstract：:In this issue of Cell Stem Cell, Saito et al. (2015) examine how leukemia-initiating cells react to metabolic stress imposed by different tissue environments. They find that inhibition of the metabolic stress sensor AMP-activated protein kinase (AMPK) led to deranged glucose metabolism and redox homeostasis, resulting...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2015.10.007
更新日期：2015-11-05 00:00:00
abstract：:Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptot...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.10.013
更新日期：2016-11-03 00:00:00
abstract：:Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by mutations in the astrocytic filament gene GFAP. While astrocytes are thought to have important roles in controlling myelination, AxD animal models do not recapitulate critical myelination phenotypes and it is therefore not c...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2018.07.009
更新日期：2018-08-02 00:00:00
abstract：:The Notch signaling pathway is activated in the majority of T cell acute lymphoblastic leukemias (T-ALL). Adding to the complexity of Notch signaling in hematopoiesis, recently in Nature, Klinakis et al. (2011) demonstrate a tumor-suppressor function for the Notch pathway in myeloid malignancy. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2011.04.010
更新日期：2011-06-03 00:00:00
abstract：:Renal pathology suggests that tubular repair results from tubular proliferation. In contrast, recent studies propose that postnatal kidney repair may involve renal stem cells. In this issue of Cell Stem Cell, Humphreys et al. (2008) use lineage tracing to genetically assess contribution of adult nontubular cells (pote...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2008.02.007
更新日期：2008-03-06 00:00:00
abstract：:Somatic cells can be induced into pluripotent stem cells (iPSCs) with a combination of four transcription factors, Oct4/Sox2/Klf4/c-Myc or Oct4/Sox2/Nanog/LIN28. This provides an enabling platform to obtain patient-specific cells for various therapeutic and research applications. However, several problems remain for t...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2008.10.004
更新日期：2008-11-06 00:00:00
abstract：:Sox family transcription factors have emerged as key regulators of multiple developmental processes, including fate determination and differentiation in multiple tissues. In this issue of Cell Stem Cell, Nowak et al. (2008) implicate Sox9 in the specification of early hair follicle stem cells and subsequent epithelial...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2008.06.014
更新日期：2008-07-03 00:00:00
abstract：:In this issue of Cell Stem Cell, Li et al. (2020) reveal pivotal roles for Lats1/2 in adult, Wnt-mediated intestinal homeostasis through TEAD-dependent and -independent transcription. Loss of Lats1/2 mobilizes a previously unrecognized YAP/TAZ-Groucho/TLE interaction to suppress Wnt/TCF-mediated transcription, thereby...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2020.04.011
更新日期：2020-05-07 00:00:00
abstract：:Oocyte defects lie at the heart of some forms of infertility and could potentially be addressed therapeutically by alternative routes for oocyte formation. Here, we describe the generation of functional human oocytes following nuclear transfer of first polar body (PB1) genomes from metaphase II (MII) oocytes into enuc...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.10.001
更新日期：2017-01-05 00:00:00
abstract：:Although the clinical outcomes of cell therapy trials have not met initial expectations, emerging evidence suggests that injury-mediated tissue damage might benefit from the delivery of cells or their secreted products. Pluripotent stem cells (PSCs) are promising cell sources primarily because of their capacity to gen...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2019.10.001
更新日期：2019-11-07 00:00:00
abstract：:A survey of U.S. stem cell scientists shows that uncertainty following the legal challenge to the Obama Administration's hESC research policy has negative scientific and economic impacts and affects a range of stem cell scientists, not just those working with hESCs. The international implications of these results are ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2011.01.002
更新日期：2011-02-04 00:00:00
abstract：:Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2017.02.010
更新日期：2017-03-02 00:00:00
abstract：:Polycomb group (PcG) proteins are essential regulators of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent domains consisting of overlapping repressive and activating histone modifications to keep them poised for activation in embryonic stem cells. Bmi1, a componen...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2010.01.005
更新日期：2010-03-05 00:00:00
abstract：:Technological limitations have hampered understanding of how individual molecules, including putative stem cell regulators, are distributed throughout tissues and stem cell niches. Here, we report adaptation of the proximity ligation assay (PLA) for large-volume, in situ imaging of individual proteins with multiple ad...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.10.003
更新日期：2019-12-05 00:00:00
abstract：:While studies of organ development have traditionally relied on model organisms, recent advances in embryonic stem cell (ESC) culture allow investigation of organogenesis in human cells. Wang et al. (2015) employ this system to map the dynamic enhancer landscape during ESC differentiation to the endoderm derivatives p...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2015.03.006
更新日期：2015-04-02 00:00:00
abstract：:To date, pluripotent epiblast stem cells (EpiSCs) had only been derived from postimplantation mouse embryos. In this issue of Cell Stem Cell, Najm et al. (2011) demonstrate that EpiSCs can be routinely derived from preimplantation embryos, showing that both human and mouse blastocysts can produce the same class of pri...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2011.02.009
更新日期：2011-03-04 00:00:00
