Enhanced engraftment of human myelofibrosis stem and progenitor cells in MISTRG mice.

Animals Hematopoietic Stem Cells Heterografts Humans Mice Mice, Inbred BALB C Mice, Inbred NOD Primary Myelofibrosis / genetics

Journal

Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425

Informations de publication

Date de publication:
09 06 2020
Historique:
received: 17 12 2019
accepted: 28 04 2020
entrez: 6 6 2020
pubmed: 6 6 2020
medline: 11 5 2021
Statut: ppublish

Résumé

The engraftment potential of myeloproliferative neoplasms in immunodeficient mice is low. We hypothesized that the physiological expression of human cytokines (macrophage colony-stimulating factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and thrombopoietin) combined with human signal regulatory protein α expression in Rag2-/-Il2rγ-/- (MISTRG) mice might provide a supportive microenvironment for the development and maintenance of hematopoietic stem and progenitor cells (HSPC) from patients with primary, post-polycythemia or post-essential thrombocythemia myelofibrosis (MF). We show that MISTRG mice, in contrast to standard immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ and Rag2-/-Il2rγ-/- mice, supported engraftment of all patient samples investigated independent of MF disease stage or risk category. Moreover, MISTRG mice exhibited significantly higher human MF engraftment levels in the bone marrow, peripheral blood, and spleen and supported secondary repopulation. Bone marrow fibrosis development was limited to 3 of 14 patient samples investigated in MISTRG mice. Disease-driving mutations were identified in all xenografts, and targeted sequencing revealed maintenance of the primary patient sample clonal composition in 7 of 8 cases. Treatment of engrafted mice with the current standard-of-care Janus kinase inhibitor ruxolitinib led to a reduction in human chimerism. In conclusion, the established MF patient-derived xenograft model supports robust engraftment of MF HSPCs and maintains the genetic complexity observed in patients. The model is suited for further testing of novel therapeutic agents to expedite their transition into clinical trials.

Identifiants

DOI: 10.1182/bloodadvances.2019001364 PMID: 32502268 PMC: PMC7284099
pubmed: 32502268
pii: S2473-9529(20)31275-1
doi: 10.1182/bloodadvances.2019001364
pmc: PMC7284099
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2477-2488

Subventions

Organisme : Cancer Research UK
ID : 29034
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L006340/1
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States

Informations de copyright

© 2020 by The American Society of Hematology.

Références

Nature. 2005 Apr 28;434(7037):1144-8
pubmed: 15793561
J Exp Med. 2016 Aug 22;213(9):1723-40
pubmed: 27481130
Blood. 2013 Feb 14;121(7):1188-99
pubmed: 23264594
Cancer Cell. 2005 Apr;7(4):387-97
pubmed: 15837627
Blood. 2001 Dec 1;98(12):3249-55
pubmed: 11719361
Blood Adv. 2019 Feb 12;3(3):268-274
pubmed: 30696625
Cell Stem Cell. 2017 Jun 1;20(6):785-800.e8
pubmed: 28457748
Leukemia. 2017 May;31(5):1136-1144
pubmed: 27807369
Haematologica. 2014 Feb;99(2):292-8
pubmed: 23911705
Blood. 2010 Jan 28;115(4):778-82
pubmed: 19965680
Blood Cancer J. 2019 Jan 25;9(2):12
pubmed: 30683837
Cell Stem Cell. 2012 Feb 3;10(2):120-36
pubmed: 22305562
Annu Rev Immunol. 2013;31:635-674
pubmed: 23330956
PLoS Med. 2006 Jul;3(7):e270
pubmed: 16834459
Semin Hematol. 2005 Oct;42(4):184-95
pubmed: 16210032
Nature. 2019 Jul;571(7765):355-360
pubmed: 31270458
Lancet. 2005 Mar 19-25;365(9464):1054-61
pubmed: 15781101
Haematologica. 2016 Jan;101(1):5-19
pubmed: 26721800
N Engl J Med. 2018 Nov 01;379(18):1711-1721
pubmed: 30380386
Mol Immunol. 2007 Apr;44(10):2497-506
pubmed: 17208301
Nat Biotechnol. 2014 Apr;32(4):364-72
pubmed: 24633240
Blood. 2014 May 29;123(22):e123-33
pubmed: 24740812
Cell Stem Cell. 2014 Aug 7;15(2):154-68
pubmed: 24953181
Nat Immunol. 2007 Dec;8(12):1313-23
pubmed: 17982459
Pharmacotherapy. 2013 Jan;33(1):84-92
pubmed: 23307549
Biol Blood Marrow Transplant. 2014 Sep;20(9):1274-81
pubmed: 24680977
Exp Hematol. 2007 Nov;35(11):1719-22
pubmed: 17976523
Blood Cancer J. 2019 Mar 29;9(4):42
pubmed: 30926777
Blood. 2018 Feb 8;131(6):649-661
pubmed: 29282219
Nat Commun. 2019 Jan 21;10(1):366
pubmed: 30664659
Blood. 2016 Oct 27;128(17):2130-2134
pubmed: 27581357
Blood. 2016 Oct 6;128(14):1829-1833
pubmed: 27543436
Blood. 2002 Nov 15;100(10):3495-503
pubmed: 12393681
N Engl J Med. 2013 Dec 19;369(25):2391-2405
pubmed: 24325359
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
J Clin Invest. 2012 Nov;122(11):3888-99
pubmed: 23023702
Nature. 2015 Jan 15;517(7534):381-5
pubmed: 25561180
Nat Med. 2016 Jul;22(7):812-21
pubmed: 27213817
Cancer Cell. 2011 Nov 15;20(5):661-73
pubmed: 22094259
N Engl J Med. 2013 Dec 19;369(25):2379-90
pubmed: 24325356
BMC Genomics. 2014 Dec 23;15:1172
pubmed: 25539684
Biol Blood Marrow Transplant. 2014 Jun;20(6):812-5
pubmed: 24589549
Mol Cell. 2019 Mar 21;73(6):1292-1305.e8
pubmed: 30765193
Eur J Cancer. 2017 May;76:100-109
pubmed: 28286286
Blood. 2014 Apr 3;123(14):2220-8
pubmed: 24478400
Nat Cell Biol. 2017 Jun;19(6):677-688
pubmed: 28481328
Blood Rev. 2017 May;31(3):139-150
pubmed: 27899218
N Engl J Med. 2005 Apr 28;352(17):1779-90
pubmed: 15858187

Auteurs

Veronika Lysenko (V)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Nicole Wildner-Verhey van Wijk (N)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Kathrin Zimmermann (K)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Marie-Christine Weller (MC)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Marco Bühler (M)

Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

Mattheus H E Wildschut (MHE)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

Patrick Schürch (P)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Christine Fritz (C)

Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

Ulrich Wagner (U)

Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

Laura Calabresi (L)

Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero, Universitaria Careggi, University of Florence, Florence, Italy.

Bethan Psaila (B)

Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine.
Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, and.
National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.

Richard A Flavell (RA)

Department of Immunobiology, Yale University, New Haven, CT.

Alessandro M Vannucchi (AM)

Center for Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero, Universitaria Careggi, University of Florence, Florence, Italy.

Adam J Mead (AJ)

Haematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine.
Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, and.
National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.

Peter J Wild (PJ)

Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany; and.

Stefan Dirnhofer (S)

Institute of Pathology, University Hospital, University of Basel, Basel, Switzerland.

Markus G Manz (MG)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

Alexandre P A Theocharides (APA)

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

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 › Eucaryotes › Animaux › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Régions du corps › Transplants › Hétérogreffes › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Enhanced engraftment of human myelofibrosis...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Maladies de la moelle osseuse › Syndromes myéloprolifératifs › Myélofibrose primitive › Enhanced engraftment of human myelofibrosis...