-
Je něco špatně v tomto záznamu ?
Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup
S. Ramamoorthy, D. Lebrecht, D. Schanze, I. Schanze, I. Wieland, G. Andrieux, P. Metzger, M. Hess, MH. Albert, A. Borkhardt, D. Bresters, J. Buechner, A. Catala, V. De Haas, M. Dworzak, M. Erlacher, H. Hasle, K. Jahnukainen, F. Locatelli, R....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
EkoEstMed-FKZ 01ZZ2015
Bundesministerium für Bildung und Forschung
MIRACUM-FKZ 01ZZ1801B
Bundesministerium für Bildung und Forschung
MyPred 01GM1911A
Bundesministerium für Bildung und Forschung
CRC/TRR167-Z01
Deutsche Forschungsgemeinschaft
CRC1160-Z02
Deutsche Forschungsgemeinschaft
CRC1453-S1
Deutsche Forschungsgemeinschaft
CRC1479-S1
Deutsche Forschungsgemeinschaft
CRC992-C05
Deutsche Forschungsgemeinschaft
DJCLS 15R/2022
José Carreras Leukämie-Stiftung
PubMed
37945316
DOI
10.1111/bjh.19190
Knihovny.cz E-zdroje
- MeSH
- dítě MeSH
- juvenilní myelomonocytární leukemie * genetika MeSH
- lidé MeSH
- mutace MeSH
- neurofibromatóza 1 * genetika MeSH
- signální transdukce MeSH
- tumor supresorové geny MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Juvenile myelomonocytic leukaemia (JMML) is characterized by gene variants that deregulate the RAS signalling pathway. Children with neurofibromatosis type 1 (NF-1) carry a defective NF1 allele in the germline and are predisposed to JMML, which presumably requires somatic inactivation of the NF1 wild-type allele. Here we examined the two-hit concept in leukaemic cells of 25 patients with JMML and NF-1. Ten patients with JMML/NF-1 exhibited a NF1 loss-of-function variant in combination with uniparental disomy of the 17q arm. Five had NF1 microdeletions combined with a pathogenic NF1 variant and nine carried two compound-heterozygous NF1 variants. We also examined 16 patients without clinical signs of NF-1 and no variation in the JMML-associated driver genes PTPN11, KRAS, NRAS or CBL (JMML-5neg) and identified eight patients with NF1 variants. Three patients had microdeletions combined with hemizygous NF1 variants, three had compound-heterozygous NF1 variants and two had heterozygous NF1 variants. In addition, we found a high incidence of secondary ASXL1 and/or SETBP1 variants in both groups. We conclude that the clinical diagnosis of JMML/NF-1 reliably indicates a NF1-driven JMML subtype, and that careful NF1 analysis should be included in the genetic workup of JMML even in the absence of clinical evidence of NF-1.
Department of Hematology and Oncology Hospital Sant Joan de Déu Barcelona Spain
Department of Pediatric Hematology and Oncology Oslo University Hospital Oslo Norway
Department of Pediatric Oncology Hematology Skåne University Hospital Lund Sweden
Department of Pediatrics Aarhus University Hospital Skejby Aarhus Denmark
Faculty of Biology University of Freiburg Freiburg Germany
German Cancer Consortium partner site Freiburg Freiburg Germany
Human Genetics University of Magdeburg Magdeburg Germany
Princess Maxima Center for Pediatric Oncology Utrecht Netherlands
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24007413
- 003
- CZ-PrNML
- 005
- 20240423155933.0
- 007
- ta
- 008
- 240412s2024 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1111/bjh.19190 $2 doi
- 035 __
- $a (PubMed)37945316
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Ramamoorthy, Senthilkumar $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 245 10
- $a Biallelic inactivation of the NF1 tumour suppressor gene in juvenile myelomonocytic leukaemia: Genetic evidence of driver function and implications for diagnostic workup / $c S. Ramamoorthy, D. Lebrecht, D. Schanze, I. Schanze, I. Wieland, G. Andrieux, P. Metzger, M. Hess, MH. Albert, A. Borkhardt, D. Bresters, J. Buechner, A. Catala, V. De Haas, M. Dworzak, M. Erlacher, H. Hasle, K. Jahnukainen, F. Locatelli, R. Masetti, J. Stary, D. Turkiewicz, L. Vinci, MW. Wlodarski, A. Yoshimi, M. Boerries, CM. Niemeyer, M. Zenker, C. Flotho
- 520 9_
- $a Juvenile myelomonocytic leukaemia (JMML) is characterized by gene variants that deregulate the RAS signalling pathway. Children with neurofibromatosis type 1 (NF-1) carry a defective NF1 allele in the germline and are predisposed to JMML, which presumably requires somatic inactivation of the NF1 wild-type allele. Here we examined the two-hit concept in leukaemic cells of 25 patients with JMML and NF-1. Ten patients with JMML/NF-1 exhibited a NF1 loss-of-function variant in combination with uniparental disomy of the 17q arm. Five had NF1 microdeletions combined with a pathogenic NF1 variant and nine carried two compound-heterozygous NF1 variants. We also examined 16 patients without clinical signs of NF-1 and no variation in the JMML-associated driver genes PTPN11, KRAS, NRAS or CBL (JMML-5neg) and identified eight patients with NF1 variants. Three patients had microdeletions combined with hemizygous NF1 variants, three had compound-heterozygous NF1 variants and two had heterozygous NF1 variants. In addition, we found a high incidence of secondary ASXL1 and/or SETBP1 variants in both groups. We conclude that the clinical diagnosis of JMML/NF-1 reliably indicates a NF1-driven JMML subtype, and that careful NF1 analysis should be included in the genetic workup of JMML even in the absence of clinical evidence of NF-1.
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a juvenilní myelomonocytární leukemie $x genetika $7 D054429
- 650 12
- $a neurofibromatóza 1 $x genetika $7 D009456
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a signální transdukce $7 D015398
- 650 _2
- $a tumor supresorové geny $7 D016147
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Lebrecht, Dirk $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Schanze, Denny $u Human Genetics, University of Magdeburg, Magdeburg, Germany
- 700 1_
- $a Schanze, Ina $u Human Genetics, University of Magdeburg, Magdeburg, Germany
- 700 1_
- $a Wieland, Ilse $u Human Genetics, University of Magdeburg, Magdeburg, Germany
- 700 1_
- $a Andrieux, Geoffroy $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Metzger, Patrick $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Hess, Maria $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Faculty of Biology, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Albert, Michael H $u Department of Pediatric Hematology and Oncology, Dr. v. Hauner Children's Hospital, University Hospital, LMU, Munich, Germany
- 700 1_
- $a Borkhardt, Arndt $u Department of Pediatric Oncology, Hematology and Immunology, University of Dusseldorf, Dusseldorf, Germany
- 700 1_
- $a Bresters, Dorine $u Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands
- 700 1_
- $a Buechner, Jochen $u Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway
- 700 1_
- $a Catala, Albert $u Department of Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
- 700 1_
- $a De Haas, Valerie $u Diagnostic Laboratory/DCOG Laboratory, Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands
- 700 1_
- $a Dworzak, Michael $u St. Anna Children's Cancer Research Institute, Vienna, Austria $u Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria $1 https://orcid.org/0000000281751097
- 700 1_
- $a Erlacher, Miriam $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Freiburg, Freiburg, Germany
- 700 1_
- $a Hasle, Henrik $u Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
- 700 1_
- $a Jahnukainen, Kirsi $u Division of Hematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Hospital, Helsinki, Finland
- 700 1_
- $a Locatelli, Franco $u Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Catholic University of the Sacred Heart, Rome, Italy $1 https://orcid.org/0000000279763654
- 700 1_
- $a Masetti, Riccardo $u Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- 700 1_
- $a Stary, Jan $u Department of Pediatric Hematology/ Oncology, Charles University and Univ Hospital Motol, Prague, Czech Republic
- 700 1_
- $a Turkiewicz, Dominik $u Department of Pediatric Oncology/Hematology, Skåne University Hospital, Lund, Sweden
- 700 1_
- $a Vinci, Luca $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Wlodarski, Marcin W $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Yoshimi, Ayami $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $1 https://orcid.org/0000000315939507
- 700 1_
- $a Boerries, Melanie $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Freiburg, Freiburg, Germany
- 700 1_
- $a Niemeyer, Charlotte M $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Freiburg, Freiburg, Germany
- 700 1_
- $a Zenker, Martin $u Human Genetics, University of Magdeburg, Magdeburg, Germany
- 700 1_
- $a Flotho, Christian $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Freiburg, Freiburg, Germany $1 https://orcid.org/0000000193670553
- 773 0_
- $w MED00009374 $t British journal of haematology $x 1365-2141 $g Roč. 204, č. 2 (2024), s. 595-605
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37945316 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240412 $b ABA008
- 991 __
- $a 20240423155929 $b ABA008
- 999 __
- $a ok $b bmc $g 2081408 $s 1217180
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 204 $c 2 $d 595-605 $e 20231109 $i 1365-2141 $m British journal of haematology $n Br J Haematol $x MED00009374
- GRA __
- $a EkoEstMed-FKZ 01ZZ2015 $p Bundesministerium für Bildung und Forschung
- GRA __
- $a MIRACUM-FKZ 01ZZ1801B $p Bundesministerium für Bildung und Forschung
- GRA __
- $a MyPred 01GM1911A $p Bundesministerium für Bildung und Forschung
- GRA __
- $a CRC/TRR167-Z01 $p Deutsche Forschungsgemeinschaft
- GRA __
- $a CRC1160-Z02 $p Deutsche Forschungsgemeinschaft
- GRA __
- $a CRC1453-S1 $p Deutsche Forschungsgemeinschaft
- GRA __
- $a CRC1479-S1 $p Deutsche Forschungsgemeinschaft
- GRA __
- $a CRC992-C05 $p Deutsche Forschungsgemeinschaft
- GRA __
- $a DJCLS 15R/2022 $p José Carreras Leukämie-Stiftung
- LZP __
- $a Pubmed-20240412
