Abstract:
:A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Witkowski MT,Dolgalev I,Evensen NA,Ma C,Chambers T,Roberts KG,Sreeram S,Dai Y,Tikhonova AN,Lasry A,Qu C,Pei D,Cheng C,Robbins GA,Pierro J,Selvaraj S,Mezzano V,Daves M,Lupo PJ,Scheurer ME,Loomis CA,Mullighan CG,doi
10.1016/j.ccell.2020.04.015subject
Has Abstractpub_date
2020-06-08 00:00:00pages
867-882.e12issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(20)30214-2journal_volume
37pub_type
杂志文章相关文献
CANCER CELL文献大全abstract::Transcription factor NF-kappaB has been implicated in cancer development due to its ability to upregulate expression of genes with potentially prooncogenic functions, such as cell cycle regulators and antiapoptotic proteins (Karin et al., 2002). A recent report by suggests that a structural motif, a death domain (DD),...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/s1535-6108(02)00213-1
更新日期:2002-12-01 00:00:00
abstract::Hepatocellular adenomas (HCAs) are clinically relevant benign liver lesions that commonly occur in women on hormonal contraceptives. In this issue of Cancer Cell, Pilati and colleagues present an integrative multi-"omics"-based analysis of HCA and identify recurrent genetic alterations associated with adenoma-carcinom...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2014.03.032
更新日期:2014-04-14 00:00:00
abstract::The COVID-19 pandemic is profoundly changing cancer researchers and cancer research. Leaders from different fields and at different career stages share their perspectives. ...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2020.10.007
更新日期:2020-11-09 00:00:00
abstract::During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2009.06.018
更新日期:2009-08-04 00:00:00
abstract::The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell, two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2014.10.008
更新日期:2014-11-10 00:00:00
abstract::Gene alterations play a prominent role in driving cancer initiation and progression. However, the genetic events that occur in normal cells prior to tumorigenesis are still unknown. Recent studies have started to map somatic mutations in normal human tissues, and here we discuss their implications for our understandin...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2020.11.002
更新日期:2020-11-17 00:00:00
abstract::Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2017.08.005
更新日期:2017-11-13 00:00:00
abstract::Here, we show that tumor ADORA1 deletion suppresses cell growth in human melanoma cell lines in vitro and tumor development in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PD-L1 levels, which inactivates cocultured T cells in vitro, compromises anti-tumor immunity in vivo, an...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2020.02.006
更新日期:2020-03-16 00:00:00
abstract::Angiogenesis is a hallmark of solid tumors, and disruption of tumor vasculature is an active anticancer therapy in some cases. Several proteins expressed on the surface of tumor endothelium have been identified during the last decade. However, due to the expression in both physiological and tumor angiogenesis, only a ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2007.05.004
更新日期:2007-06-01 00:00:00
abstract::Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tu...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2004.07.009
更新日期:2004-08-01 00:00:00
abstract::The TFAP2C/AP-2γ transcription factor regulates luminal breast cancer genes, and loss of TFAP2C induces epithelial-mesenchymal transition. By contrast, the highly homologous family member, TFAP2A, lacks transcriptional activity at luminal gene promoters. A detailed structure-function analysis identified that sumoylati...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2014.04.008
更新日期:2014-06-16 00:00:00
abstract::Immune checkpoint-blockade treatments targeting PD-1/PD-L1 have revolutionized cancer therapy. Hence, understanding the regulation of PD-L1 expression has major clinical relevance. In this issue of Cancer Cell, Lim et al. report that inflammation-induced and NF-κB-driven expression of deubiquitinating enzyme CSN5 lead...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2016.11.013
更新日期:2016-12-12 00:00:00
abstract::One of the biggest challenges in treating acute myeloid leukemia (AML) is relapse of aggressive disease after treatment. In this issue of Cancer Cell, Boyd et al. characterize a molecularly distinct population of chemotherapy-induced transient leukemic regenerating cells (LRCs), which can be exploited to prevent AML r...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2018.08.012
更新日期:2018-09-10 00:00:00
abstract::In the July issue of Nature Medicine, Massagué and colleagues define a biphasic role for the extracellular matrix protein tenascin C as a metastatic niche component in lung colonization by breast cancer cells. These results provide a rationale for designing therapies targeting metastatic progression by disrupting its ...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2011.08.004
更新日期:2011-08-16 00:00:00
abstract::Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR). In contrast, Myc activation-although producing a DDR as well-is known to primarily elicit an apoptotic countermeasure. Using the Emu-my...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2009.12.043
更新日期:2010-03-16 00:00:00
abstract::ARID1A encodes an SWI/SNF chromatin-remodeling factor and is frequently mutated in various cancers. This study demonstrates that ARID1A-deficient cancer cells are specifically vulnerable to inhibition of the antioxidant glutathione (GSH) and the glutamate-cysteine ligase synthetase catalytic subunit (GCLC), a rate-lim...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2018.12.009
更新日期:2019-02-11 00:00:00
abstract::Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causi...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2018.03.021
更新日期:2018-05-14 00:00:00
abstract::Even in the presence of an adequate oxygen supply, many tumors metabolize the majority of the glucose they take up through glycolysis. It has been a long-held belief that this glycolytic phenotype is due to cancer-specific defects in mitochondrial oxidative phosphorylation. In this issue of Cancer Cell, Fantin et al. ...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2006.05.012
更新日期:2006-06-01 00:00:00
abstract::CAR-engineered T cell immunotherapy has proven transformative in selected hematological malignancies. However, solid tumors largely remain impervious to these approaches. In addressing this challenge, Srivastava et al. in this issue demonstrate that oxaliplatin-based lymphodepleting chemotherapy promotes enhanced CAR ...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2020.12.019
更新日期:2020-12-30 00:00:00
abstract::The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels o...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2016.03.002
更新日期:2016-04-11 00:00:00
abstract::The hedgehog (Hh) signaling pathway plays many roles in invertebrate and vertebrate development. For example, specific inhibition of sonic Hh expression is critical during early stages of pancreas organogenesis, but an active Hh pathway appears to be required for maintenance of adult endocrine functions. Mutational in...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/s1535-6108(03)00246-0
更新日期:2003-10-01 00:00:00
abstract::The tumor suppressor cylindromatosis (CYLD) inhibits the NFκB and mitogen-activated protein kinase (MAPK) activation pathways by deubiquitinating upstream regulatory factors. Here we show that liver-specific disruption of CYLD triggers hepatocyte cell death in the periportal area via spontaneous and chronic activation...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2012.04.026
更新日期:2012-06-12 00:00:00
abstract::The molecular mechanisms regulating leukemia-initiating cell (LIC) function are of important clinical significance. We use chronic myelogenous leukemia (CML) as a model of LIC-dependent malignancy and identify the interaction between the ubiquitin ligase Fbw7 and its substrate c-Myc as a regulator of LIC homeostasis. ...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2013.01.025
更新日期:2013-03-18 00:00:00
abstract::MicroRNAs (miRNA) are mostly downregulated in cancer. However, the mechanism underlying this phenomenon and the precise consequence in tumorigenesis remain obscure. Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation b...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccell.2016.10.001
更新日期:2016-11-14 00:00:00
abstract::The role of the von Hippel-Lindau tumor suppressor protein (pVHL) in kidney cancer has provided a rationale for treating this disease with hypoxia-inducible factor (HIF) antagonists. In this issue, Simon and coworkers show that the molecular signature of VHL(-/-) kidney cancers is profoundly influenced by whether they...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccr.2008.11.005
更新日期:2008-12-09 00:00:00
abstract::Homeobox domain-containing transcription factors are important regulators of hematopoiesis. Here, we report that increased levels of nonclustered H2.0-like homeobox (HLX) lead to loss of functional hematopoietic stem cells and formation of aberrant progenitors with unlimited serial clonogenicity and blocked differenti...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2012.06.027
更新日期:2012-08-14 00:00:00
abstract::Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte li...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2012.11.020
更新日期:2013-03-18 00:00:00
abstract::Immune cells' metabolism influences their differentiation and function. Given that a complex interplay of environmental factors within the tumor microenvironment (TME) can have a profound impact on the metabolic activities of immune, stromal, and tumor cell types, there is emerging interest to advance understanding of...
journal_title:Cancer cell
pub_type: 杂志文章,评审
doi:10.1016/j.ccell.2020.09.004
更新日期:2021-01-11 00:00:00
abstract::E proteins and their functional antagonists, the ID proteins, have significant roles in normal hematopoiesis. In this issue of Cancer Cell, Ghisi et al. show that high ID2 levels antagonize self-renewal and promote differentiation of leukemic stem cells in the MLL-translocated molecular subtype of acute myeloid leukem...
journal_title:Cancer cell
pub_type: 评论,杂志文章
doi:10.1016/j.ccell.2016.06.006
更新日期:2016-07-11 00:00:00
abstract::Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissect...
journal_title:Cancer cell
pub_type: 杂志文章
doi:10.1016/j.ccr.2009.10.018
更新日期:2009-12-08 00:00:00