Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL

B. Bornhauser, G. Cario, A. Rinaldi, T. Risch, V. Rodriguez Martinez, M. Schütte, HJ. Warnatz, N. Scheidegger, P. Mirkowska, M. Temperli, C. Möller, A. Schumich, M. Dworzak, A. Attarbaschi, M. Brüggemann, M. Ritgen, E. Mejstrikova, A. Hofmann, B....

. 2020 ; 4 (17) : 4052-4064. [pub] 20200908

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21020142

Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based on persistence of minimal residual disease (MRD). New insights into biological features that are associated with MRD are needed. Here, we identify the glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting the cell surface proteome of MRD very high-risk (HR) B-cell precursor (BCP) ALL using a chemoproteomics strategy. The correlation between VNN2 transcript and surface protein expression enabled a retrospective analysis (ALL-BFM 2000; N = 770 cases) using quantitative polymerase chain reaction to confirm the association of VNN2 with MRD and independent prediction of worse outcome. Using flow cytometry, we detected VNN2 expression in 2 waves, in human adult bone marrow stem and progenitor cells and in the mature myeloid compartment, in line with proposed roles for fetal hematopoietic stem cells and inflammation. Prospective validation by flow cytometry in the ongoing clinical trial (AIEOP-BFM 2009) identified 10% (103/1069) of VNN2+ BCP ALL patients at first diagnosis, primarily in the MRD MR (48/103, 47%) and HR (37/103, 36%) groups, across various cytogenetic subtypes. We also detected frequent mutations in epigenetic regulators in VNN2+ ALLs, including histone H3 methyltransferases MLL2, SETD2, and EZH2 and demethylase KDM6A. Inactivation of the VNN2 gene did not impair leukemia repopulation capacity in xenografts. Taken together, VNN2 marks a cellular state of increased resistance to chemotherapy that warrants further investigations. Therefore, this marker should be included in diagnostic flow cytometry panels.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21020142
003      
CZ-PrNML
005      
20210830101744.0
007      
ta
008      
210728s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1182/bloodadvances.2019000938 $2 doi
035    __
$a (PubMed)32853382
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Bornhauser, Beat $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
245    14
$a The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL / $c B. Bornhauser, G. Cario, A. Rinaldi, T. Risch, V. Rodriguez Martinez, M. Schütte, HJ. Warnatz, N. Scheidegger, P. Mirkowska, M. Temperli, C. Möller, A. Schumich, M. Dworzak, A. Attarbaschi, M. Brüggemann, M. Ritgen, E. Mejstrikova, A. Hofmann, B. Buldini, P. Scarparo, G. Basso, O. Maglia, G. Gaipa, TL. Skoblyn, G. Te Kronnie, E. Vendramini, R. Panzer-Grümayer, MJ. Barz, B. Marovca, M. Hauri-Hohl, F. Niggli, C. Eckert, M. Schrappe, M. Stanulla, M. Zimmermann, B. Wollscheid, ML. Yaspo, JP. Bourquin
520    9_
$a Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based on persistence of minimal residual disease (MRD). New insights into biological features that are associated with MRD are needed. Here, we identify the glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting the cell surface proteome of MRD very high-risk (HR) B-cell precursor (BCP) ALL using a chemoproteomics strategy. The correlation between VNN2 transcript and surface protein expression enabled a retrospective analysis (ALL-BFM 2000; N = 770 cases) using quantitative polymerase chain reaction to confirm the association of VNN2 with MRD and independent prediction of worse outcome. Using flow cytometry, we detected VNN2 expression in 2 waves, in human adult bone marrow stem and progenitor cells and in the mature myeloid compartment, in line with proposed roles for fetal hematopoietic stem cells and inflammation. Prospective validation by flow cytometry in the ongoing clinical trial (AIEOP-BFM 2009) identified 10% (103/1069) of VNN2+ BCP ALL patients at first diagnosis, primarily in the MRD MR (48/103, 47%) and HR (37/103, 36%) groups, across various cytogenetic subtypes. We also detected frequent mutations in epigenetic regulators in VNN2+ ALLs, including histone H3 methyltransferases MLL2, SETD2, and EZH2 and demethylase KDM6A. Inactivation of the VNN2 gene did not impair leukemia repopulation capacity in xenografts. Taken together, VNN2 marks a cellular state of increased resistance to chemotherapy that warrants further investigations. Therefore, this marker should be included in diagnostic flow cytometry panels.
650    _2
$a amidohydrolasy $x terapeutické užití $7 D000581
650    _2
$a protokoly protinádorové kombinované chemoterapie $7 D000971
650    _2
$a B-lymfocyty $7 D001402
650    _2
$a molekuly buněčné adheze $7 D015815
650    _2
$a dítě $7 D002648
650    12
$a chemorezistence $x genetika $7 D019008
650    _2
$a GPI-vázané proteiny $7 D058851
650    _2
$a hematopoetické kmenové buňky $7 D006412
650    _2
$a lidé $7 D006801
650    12
$a akutní lymfatická leukemie $x farmakoterapie $7 D054198
650    _2
$a prospektivní studie $7 D011446
650    _2
$a retrospektivní studie $7 D012189
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Cario, Gunnar $u Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
700    1_
$a Rinaldi, Anna $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Risch, Thomas $u Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
700    1_
$a Rodriguez Martinez, Virginia $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Schütte, Moritz $u Alacris Theranostics, Berlin, Germany
700    1_
$a Warnatz, Hans-Jörg $u Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
700    1_
$a Scheidegger, Nastassja $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Mirkowska, Paulina $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Temperli, Martina $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Möller, Claudia $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Schumich, Angela $u St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria
700    1_
$a Dworzak, Michael $u St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria
700    1_
$a Attarbaschi, Andishe $u St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria
700    1_
$a Brüggemann, Monika $u Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany
700    1_
$a Ritgen, Mathias $u Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany
700    1_
$a Mejstrikova, Ester $u Department of Pediatric Hematology and Oncology, Charles University Hospital Motol, Prague, Czech Republic
700    1_
$a Hofmann, Andreas $u Department of Health Sciences and Technology and Institute for Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
700    1_
$a Buldini, Barbara $u Department of Women's and Children's Health, University of Padova, Padova, Italy
700    1_
$a Scarparo, Pamela $u Department of Women's and Children's Health, University of Padova, Padova, Italy
700    1_
$a Basso, Giuseppe $u Department of Women's and Children's Health, University of Padova, Padova, Italy $u Italian Institute for Genomic Medicine, Turin, Italy
700    1_
$a Maglia, Oscar $u M. Tettamanti Research Center, University of Milano Bicocca, Monza, Italy
700    1_
$a Gaipa, Giuseppe $u M. Tettamanti Research Center, University of Milano Bicocca, Monza, Italy
700    1_
$a Skoblyn, Tessa-Lara $u Pediatric Hematology and Oncology, Charité University Hospital, Berlin, Germany
700    1_
$a Te Kronnie, Geertruij $u Department of Women's and Children's Health, University of Padova, Padova, Italy
700    1_
$a Vendramini, Elena $u Department of Women's and Children's Health, University of Padova, Padova, Italy
700    1_
$a Panzer-Grümayer, Renate $u St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria
700    1_
$a Barz, Malwine Jeanette $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Marovca, Blerim $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Hauri-Hohl, Mathias $u Department of Stem Cell Transplantation, University Children's Hospital Zurich, Zurich, Switzerland; and
700    1_
$a Niggli, Felix $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
700    1_
$a Eckert, Cornelia $u Pediatric Hematology and Oncology, Charité University Hospital, Berlin, Germany
700    1_
$a Schrappe, Martin $u Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
700    1_
$a Stanulla, Martin $u Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
700    1_
$a Zimmermann, Martin $u Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
700    1_
$a Wollscheid, Bernd $u Department of Health Sciences and Technology and Institute for Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
700    1_
$a Yaspo, Marie-Laure $u Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
700    1_
$a Bourquin, Jean-Pierre $u Department of Oncology, University Children's Hospital Zurich and Children's Research Center, Zurich, Switzerland
773    0_
$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 4, č. 17 (2020), s. 4052-4064
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32853382 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830101744 $b ABA008
999    __
$a ok $b bmc $g 1690848 $s 1140588
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 4 $c 17 $d 4052-4064 $e 20200908 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912
LZP    __
$a Pubmed-20210728

Najít záznam

Citační ukazatele

Možnosti archivace