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

Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells

J. Baumeister, T. Maié, N. Chatain, L. Gan, B. Weinbergerova, MAS. de Toledo, J. Eschweiler, A. Maurer, J. Mayer, B. Kubesova, Z. Racil, A. Schuppert, I. Costa, S. Koschmieder, TH. Brümmendorf, D. Gezer

. 2021 ; 100 (12) : 2943-2956. [pub] 20210814

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22003049

Grantová podpora
KO2155/6-1 deutsche forschungsgemeinschaft
BR1782/5-1 deutsche forschungsgemeinschaft
KO2155/7-1 deutsche forschungsgemeinschaft
GE2811/4-1 deutsche forschungsgemeinschaft
grant O1-6 interdisziplinäres zentrum für klinische forschung, universitätsklinikum würzburg
00023736 ministerstvo zdravotnictví ceské republiky
65269705 ministerstvo zdravotnictví ceské republiky

Myeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing-associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22003049
003      
CZ-PrNML
005      
20220127150719.0
007      
ta
008      
220113s2021 gw f 000 0|eng||
009      
AR
024    7_
$a 10.1007/s00277-021-04615-8 $2 doi
035    __
$a (PubMed)34390367
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a gw
100    1_
$a Baumeister, Julian $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
245    10
$a Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells / $c J. Baumeister, T. Maié, N. Chatain, L. Gan, B. Weinbergerova, MAS. de Toledo, J. Eschweiler, A. Maurer, J. Mayer, B. Kubesova, Z. Racil, A. Schuppert, I. Costa, S. Koschmieder, TH. Brümmendorf, D. Gezer
520    9_
$a Myeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing-associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN.
650    _2
$a antigeny CD34 $x genetika $7 D018952
650    _2
$a regulace genové exprese u nádorů $7 D015972
650    _2
$a lidé $7 D006801
650    _2
$a myeloproliferativní poruchy $x genetika $7 D009196
650    _2
$a polycythaemia vera $x genetika $7 D011087
650    _2
$a primární myelofibróza $x genetika $7 D055728
650    _2
$a esenciální trombocytemie $x genetika $7 D013920
650    12
$a transkriptom $7 D059467
655    _2
$a časopisecké články $7 D016428
700    1_
$a Maié, Tiago $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany $u Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany
700    1_
$a Chatain, Nicolas $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
700    1_
$a Gan, Lin $u IZKF Genomics Core Facility, RWTH Aachen University Medical School, Aachen, Germany
700    1_
$a Weinbergerova, Barbora $u Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic
700    1_
$a de Toledo, Marcelo A S $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
700    1_
$a Eschweiler, Jörg $u Department of Orthopedic Surgery, University Hospital RWTH Aachen, Aachen, Germany
700    1_
$a Maurer, Angela $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
700    1_
$a Mayer, Jiri $u Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic
700    1_
$a Kubesova, Blanka $u Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic
700    1_
$a Racil, Zdenek $u Institute of Hematology and Blood Transfusion, Prague, Czech Republic
700    1_
$a Schuppert, Andreas $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany $u Joint Research Center for Computational Biomedicine, RWTH Aachen, Aachen, Germany
700    1_
$a Costa, Ivan $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany $u Institute for Computational Genomics, RWTH Aachen University, Aachen, Germany
700    1_
$a Koschmieder, Steffen $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
700    1_
$a Brümmendorf, Tim H $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany
700    1_
$a Gezer, Deniz $u Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany. dgezer@ukaachen.de $u Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO ABCD), Aachen, Germany. dgezer@ukaachen.de
773    0_
$w MED00000424 $t Annals of hematology $x 1432-0584 $g Roč. 100, č. 12 (2021), s. 2943-2956
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34390367 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220113 $b ABA008
991    __
$a 20220127150715 $b ABA008
999    __
$a ok $b bmc $g 1750730 $s 1154198
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 100 $c 12 $d 2943-2956 $e 20210814 $i 1432-0584 $m Annals of hematology $n Ann Hematol $x MED00000424
GRA    __
$a KO2155/6-1 $p deutsche forschungsgemeinschaft
GRA    __
$a BR1782/5-1 $p deutsche forschungsgemeinschaft
GRA    __
$a KO2155/7-1 $p deutsche forschungsgemeinschaft
GRA    __
$a GE2811/4-1 $p deutsche forschungsgemeinschaft
GRA    __
$a grant O1-6 $p interdisziplinäres zentrum für klinische forschung, universitätsklinikum würzburg
GRA    __
$a 00023736 $p ministerstvo zdravotnictví ceské republiky
GRA    __
$a 65269705 $p ministerstvo zdravotnictví ceské republiky
LZP    __
$a Pubmed-20220113

Najít záznam

Citační ukazatele

Možnosti archivace