Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma.

Anaplastic Lymphoma Kinase / metabolism Animals CCAAT-Enhancer-Binding Protein-beta / metabolism Cell Line, Tumor Cell Proliferation Cell Survival Cytoskeletal Proteins / metabolism Down-Regulation Enzyme Activation Extracellular Signal-Regulated MAP Kinases / metabolism Guanosine Triphosphate / metabolism Humans Intracellular Signaling Peptides and Proteins / metabolism Kaplan-Meier Estimate Lymphoma, T-Cell / enzymology MAP Kinase Signaling System Mice Protein Binding STAT3 Transcription Factor / metabolism T-Lymphocytes / immunology Tumor Suppressor Proteins / metabolism Wiskott-Aldrich Syndrome Protein / deficiency cdc42 GTP-Binding Protein / metabolism

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
01 2019
Historique:
received: 03 12 2017
accepted: 25 09 2018
pubmed: 5 12 2018
medline: 11 5 2019
entrez: 5 12 2018
Statut: ppublish

Résumé

In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-β. ALK+ lymphomas were accelerated in WASP- and WIP-deficient mice. In the absence of WASP, active GTP-bound CDC42 was increased and the genetic deletion of one CDC42 allele was sufficient to impair lymphoma growth. WASP-deficient lymphoma showed increased mitogen-activated protein kinase (MAPK) pathway activation that could be exploited as a therapeutic vulnerability. Our findings demonstrate that WASP and WIP are tumor suppressors in T cell lymphoma and suggest that MAP-kinase kinase (MEK) inhibitors combined with ALK inhibitors could achieve a more potent therapeutic effect in ALK+ ALCL.

Identifiants

DOI: 10.1038/s41591-018-0262-9 PMID: 30510251 PMC: PMC6556382
pubmed: 30510251
doi: 10.1038/s41591-018-0262-9
pii: 10.1038/s41591-018-0262-9
pmc: PMC6556382
mid: NIHMS1020071
doi:

Substances chimiques

CCAAT-Enhancer-Binding Protein-beta 0
CEBPB protein, human 0
Cytoskeletal Proteins 0
Intracellular Signaling Peptides and Proteins 0
STAT3 Transcription Factor 0
Tumor Suppressor Proteins 0
WAS protein, human 0
WIPF1 protein, human 0
Wiskott-Aldrich Syndrome Protein 0
Guanosine Triphosphate 86-01-1
ALK protein, human EC 2.7.10.1
Anaplastic Lymphoma Kinase EC 2.7.10.1
Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24
cdc42 GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

130-140

Subventions

Organisme : NCI NIH HHS
ID : DP2 CA195762
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA196703
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States

Références

Sullivan, K. E., Mullen, C. A., Blaese, R. M. & Winkelstein, J. A. A multiinstitutional survey of the Wiskott–Aldrich syndrome. J. Pediatr. 125, 876–885 (1994).
doi: 10.1016/S0022-3476(05)82002-5
Anton, I. M. et al. WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation. Immunity 16, 193–204 (2002).
doi: 10.1016/S1074-7613(02)00268-6
de la Fuente, M. A. et al. WIP is a chaperone for Wiskott–Aldrich syndrome protein (WASP). Proc. Natl Acad. Sci. USA 104, 926–931 (2007).
doi: 10.1073/pnas.0610275104
Ramesh, N. & Geha, R. Recent advances in the biology of WASP and WIP. Immunol. Res. 44, 99–111 (2009).
doi: 10.1007/s12026-008-8086-1
Ramesh, N., Anton, I. M., Hartwig, J. H. & Geha, R. S. WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. Proc. Natl Acad. Sci. USA 94, 14671–14676 (1997).
doi: 10.1073/pnas.94.26.14671
Abdul-Manan, N. et al. Structure of Cdc42 in complex with the GTPase-binding domain of the ‘Wiskott–Aldrich syndrome’ protein. Nature 399, 379–383 (1999).
doi: 10.1038/20726
Thrasher, A. J. & Burns, S. O. WASP: a key immunological multitasker. Nat. Rev. Immunol. 10, 182–192 (2010).
doi: 10.1038/nri2724
Massaad, M. J., Ramesh, N. & Geha, R. S. Wiskott–Aldrich syndrome: a comprehensive review. Ann. N. Y. Acad. Sci. 1285, 26–43 (2013).
doi: 10.1111/nyas.12049
Snapper, S. B. et al. Wiskott–Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9, 81–91 (1998).
doi: 10.1016/S1074-7613(00)80590-7
Ochs, H. D. & Thrasher, A. J. The Wiskott–Aldrich syndrome. J. Allergy Clin. Immunol. 117, 725–738 (2006). quiz 739.
doi: 10.1016/j.jaci.2006.02.005
Recher, M. et al. B cell-intrinsic deficiency of the Wiskott–Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice. Blood 119, 2819–2828 (2012).
doi: 10.1182/blood-2011-09-379412
Boddicker, R. L., Razidlo, G. L. & Feldman, A. L. Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas. Small GTPases 29, 1–7 (2016).
Scarfo, I. et al. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts. Blood 127, 221–232 (2016).
doi: 10.1182/blood-2014-12-614503
Crescenzo, R. et al. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 27, 516–532 (2015).
doi: 10.1016/j.ccell.2015.03.006
Parrilla Castellar, E. R. et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood 124, 1473–1480 (2014).
doi: 10.1182/blood-2014-04-571091
Werner, M. T., Zhao, C., Zhang, Q. & Wasik, M. A. Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target. Blood 129, 823–831 (2017).
doi: 10.1182/blood-2016-05-717793
Yoo, H. Y. et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat. Genet. 46, 371–375 (2014).
doi: 10.1038/ng.2916
Sakata-Yanagimoto, M. et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat. Genet. 46, 171–175 (2014).
doi: 10.1038/ng.2872
Palomero, T. et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat. Genet. 46, 166–170 (2014).
doi: 10.1038/ng.2873
Abate, F. et al. Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. Proc. Natl Acad. Sci. USA 114, 764–769 (2017).
doi: 10.1073/pnas.1608839114
Ambrogio, C. et al. The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation. Cancer Res. 68, 8899–8907 (2008).
doi: 10.1158/0008-5472.CAN-08-2568
Colomba, A. et al. Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas. Oncogene 27, 2728–2736 (2008).
doi: 10.1038/sj.onc.1210921
Choudhari, R. et al. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice. Blood 127, 1297–1306 (2016).
doi: 10.1182/blood-2015-11-683052
Swerdlow, S. H. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127, 2375–2390 (2016).
doi: 10.1182/blood-2016-01-643569
Chiarle, R. et al. NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors. Blood 101, 1919–1927 (2003).
doi: 10.1182/blood-2002-05-1343
Lanzi, G. et al. A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J. Exp. Med. 209, 29–34 (2012).
doi: 10.1084/jem.20110896
Al-Mousa, H. et al. Hematopoietic stem cell transplantation corrects WIP deficiency. J. Allergy Clin. Immunol. 139, 1039–1040 e1034 (2017).
doi: 10.1016/j.jaci.2016.08.036
Notarangelo, L. D., Notarangelo, L. D. & Ochs, H. D. WASP and the phenotypic range associated with deficiency. Curr. Opin. Allergy. Clin. Immunol. 5, 485–490 (2005).
doi: 10.1097/01.all.0000191243.25757.ce
Hill, C. S., Wynne, J. & Treisman, R. The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell 81, 1159–1170 (1995).
doi: 10.1016/S0092-8674(05)80020-0
Ambrogio, C. et al. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Res. 69, 8611–8619 (2009).
doi: 10.1158/0008-5472.CAN-09-2655
Hassler, M. R. et al. Insights into the pathogenesis of anaplastic large-cell lymphoma through genome-wide DNA methylation profiling. Cell Rep. 17, 596–608 (2016).
doi: 10.1016/j.celrep.2016.09.018
Piva, R. et al. Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas. Blood 107, 689–697 (2006).
doi: 10.1182/blood-2005-05-2125
Gambacorti Passerini, C. et al. Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. J. Natl Cancer. Inst. 106, djt378 (2014).
doi: 10.1093/jnci/djt378
Hrustanovic, G. et al. RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer. Nat. Med. 21, 1038–1047 (2015).
doi: 10.1038/nm.3930
Rivers, E. & Thrasher, A. J. Wiskott–Aldrich syndrome protein: emerging mechanisms in immunity. Eur. J. Immunol. 47, 1857–1866 (2017).
doi: 10.1002/eji.201646715
Chiarle, R. et al. Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target. Nat. Med. 11, 623–629 (2005).
doi: 10.1038/nm1249
Watanabe, Y. et al. T-cell receptor ligation causes Wiskott–Aldrich syndrome protein degradation and F-actin assembly downregulation. J. Allergy Clin. Immunol. 132, 648–655 e641 (2013).
doi: 10.1016/j.jaci.2013.03.046
Murga-Zamalloa, C. A. et al. NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma. Oncogene 36, 2085–2094 (2017).
doi: 10.1038/onc.2016.366
Zhang, J. et al. Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway. FASEB J 31, 4277–4285 (2017).
doi: 10.1096/fj.201700179R
McGavin, M. K. et al. The intersectin 2 adaptor links Wiskott Aldrich Syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis. J. Exp. Med. 194, 1777–1787 (2001).
doi: 10.1084/jem.194.12.1777
Wu, X. et al. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin. Genes Dev. 20, 571–585 (2006).
doi: 10.1101/gad.361406
Facchetti, F. et al. Defective actin polymerization in EBV-transformed B-cell lines from patients with the Wiskott–Aldrich syndrome. J. Pathol. 185, 99–107 (1998).
doi: 10.1002/(SICI)1096-9896(199805)185:1<99::AID-PATH48>3.0.CO;2-L
Martinengo, C. et al. ALK-dependent control of hypoxia inducible factors mediates tumor growth and metastasis. Cancer Res. 74, 6094–106 (2014).
doi: 10.1158/0008-5472.CAN-14-0268
Piva, R. et al. Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes. J. Clin. Invest. 116, 3171–3182 (2006).
doi: 10.1172/JCI29401
Ceccon, M. et al. Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency. Oncogene 35, 3854–3865 (2016).
doi: 10.1038/onc.2015.456
Orlando, D. A. et al. Quantitative ChIP-seq normalization reveals global modulation of the epigenome. Cell reports 9, 1163–1170 (2014).
doi: 10.1016/j.celrep.2014.10.018
Mansour, M. R. et al. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science 346, 1373–1377 (2014).
doi: 10.1126/science.1259037
Manser, M. et al. ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis. Sci. Rep. 7, 43345 (2017).
doi: 10.1038/srep43345
Thurman, R. E. et al. The accessible chromatin landscape of the human genome. Nature 489, 75–82 (2012).
doi: 10.1038/nature11232
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
doi: 10.1038/nmeth.1923
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
doi: 10.1093/bioinformatics/btq033
Kuhn, R. M., Haussler, D. & Kent, W. J. The UCSC genome browser and associated tools. Brief. Bioinform. 14, 144–161 (2013).
doi: 10.1093/bib/bbs038
Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome. Biol. 9, R137 (2008).
doi: 10.1186/gb-2008-9-9-r137
Shen, L., Shao, N., Liu, X. & Nestler, E. ngs.plot: quick mining and visualization of next-generation sequencing data by integrating genomic databases. BMC Genomics 15, 284 (2014).
doi: 10.1186/1471-2164-15-284
Ambrogio, C. et al. Kras dimerization impacts MEK inhibitor sensitivity and oncogenic activity of mutant KRAS. Cell 172, 857–868 e815 (2018).
doi: 10.1016/j.cell.2017.12.020

Auteurs

Matteo Menotti (M)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Cell Signalling Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.

Chiara Ambrogio (C)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
ORCID: 0000-0003-4122-701X

Taek-Chin Cheong (TC)

Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Chiara Pighi (C)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Ines Mota (I)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Seth H Cassel (SH)

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Biomedical and Biological Sciences Program, Harvard Medical School, Boston, MA, USA.
Medical Scientist Training Program, Harvard Medical School, Boston, MA, USA.

Mara Compagno (M)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Qi Wang (Q)

Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Riccardo Dall'Olio (R)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Valerio G Minero (VG)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Teresa Poggio (T)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Geeta Geeta Sharma (GG)

School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
ORCID: 0000-0003-4144-2799

Enrico Patrucco (E)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Cristina Mastini (C)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Ramesh Choudhari (R)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Center of Emphasis in Cancer, Paul L. Foster School of Medicine, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA.

Achille Pich (A)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Alberto Zamo (A)

Department of Oncology, University of Torino, Torino, Italy.

Roberto Piva (R)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Silvia Giliani (S)

Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Luca Mologni (L)

School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.

Clayton K Collings (CK)

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Cigall Kadoch (C)

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-4058-5985

Carlo Gambacorti-Passerini (C)

School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.

Luigi D Notarangelo (LD)

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-8335-0262

Ines M Anton (IM)

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain.

Claudia Voena (C)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy. claudia.voena@unito.it.
ORCID: 0000-0002-1324-1431

Roberto Chiarle (R)

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy. roberto.chiarle@childrens.harvard.edu.
Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. roberto.chiarle@childrens.harvard.edu.
ORCID: 0000-0003-1564-8531

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs à activité tyrosine kinase › Kinase du lymphome anaplasique › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Eucaryotes › Animaux › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Protéines liant les séquences stimulatrices de type CCAAT › Protéine bêta de liaison aux séquences stimulatrices de type CCAAT › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Métabolisme › Activation enzymatique › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › Extracellular Signal-Regulated MAP Kinases › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides guanyliques › Guanosine triphosphate › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Estimation de Kaplan-Meier › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome T › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-3 › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines des microfilaments › Famille de protéines du syndrome de Wiskott-Aldrich › Protéine du syndrome de Wiskott-Aldrich › Wiskott-Aldrich syndrome protein (WASP) is a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines G › Protéines G monomériques › Protéines G rho › Protéine G cdc42 › Wiskott-Aldrich syndrome protein (WASP) is a...