Association of unbalanced translocation der(1;7) with germline GATA2 mutations
Authors: Emilia J. Kozyra, Gudrun Göhring, Dennis D. Hickstein, Katherine R. Calvo, Courtney D. DiNardo, Michael Dworzak, Valerie de Haas, Jan Starý, Henrik Hasle, Akiko Shimamura, Mark D. Fleming, Hiroto Inaba, Sara Lewis, Amy P. Hsu, Steven M. Holland, Danielle E. Arnold, Cristina Mecucci, Siobán B. Keel, Alison A. Bertuch, Kiran Tawana, Shlomit Barzilai, Shinsuke Hirabayashi, Masahiro Onozawa, Shaohua Lei, Helena Alaiz, Hajnalka Andrikovics, David Betts, Berna H. Beverloo, Jochen Buechner, Martin Čermák, José Cervera, Olga Haus, Kirsi Jahnukainen, Kalliopi N. Manola, Karin Nebral, Francesco Pasquali, Joelle Tchinda, Dominik Turkiewicz, Nadine Van Roy, Zuzana Zemanova, Victor B. Pastor, Brigitte Strahm, Peter Noellke, Charlotte M. Niemeyer, Brigitte Schlegelberger, Ayami Yoshimi, Marcin W. Wlodarski
Journal: Blood (2021)

Letter to Blood| December 9, 2021 Association of unbalanced translocation der(1;7) with germline GATA2 mutations Emilia J. Kozyra, Emilia J. Kozyra Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, andFaculty of Biology, University of Freiburg, Freiburg, Germany; https://orcid.org/0000-0003-1107-8818 Search for other works by this author on: This Site PubMed Google Scholar Gudrun Göhring, Gudrun Göhring Department of Human Genetics, Hannover Medical School, Hannover, Germany; Search for other works by this author on: This Site PubMed Google Scholar Dennis D. Hickstein, Dennis D. Hickstein Immune Deficiency–Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Search for other works by this author on: This Site PubMed Google Scholar Katherine R. Calvo, Katherine R. Calvo Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD; Search for other works by this author on: This Site PubMed Google Scholar Courtney D. DiNardo, Courtney D. DiNardo Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX; https://orcid.org/0000-0001-9003-0390 Search for other works by this author on: This Site PubMed Google Scholar Michael Dworzak, Michael Dworzak St. Anna Childreńs Hospital and Cancer Research Institute, Pediatric Clinic, Medical University of Vienna, Vienna, Austria; Search for other works by this author on: This Site PubMed Google Scholar Valerie de Haas, Valerie de Haas Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands; https://orcid.org/0000-0003-0339-6816 Search for other works by this author on: This Site PubMed Google Scholar Jan Starý, Jan Starý Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic; Search for other works by this author on: This Site PubMed Google Scholar Henrik Hasle, Henrik Hasle Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark; Search for other works by this author on: This Site PubMed Google Scholar Akiko Shimamura, Akiko Shimamura Dana-Farber and Boston Children's Cancer and Blood Disorders Center, Boston, MA; https://orcid.org/0000-0002-4683-9958 Search for other works by this author on: This Site PubMed Google Scholar Mark D. Fleming, Mark D. Fleming Department of Pathology, Boston Children's Hospital, Boston, MA; https://orcid.org/0000-0003-0948-4024 Search for other works by this author on: This Site PubMed Google Scholar Hiroto Inaba, Hiroto Inaba Department of Oncology and Search for other works by this author on: This Site PubMed Google Scholar Sara Lewis, Sara Lewis Department of Hematology, St Jude Children's Research Hospital, Memphis, TN; Search for other works by this author on: This Site PubMed Google Scholar Amy P. Hsu, Amy P. Hsu Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; https://orcid.org/0000-0001-6841-2122 Search for other works by this author on: This Site PubMed Google Scholar Steven M. Holland, Steven M. Holland Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Search for other works by this author on: This Site PubMed Google Scholar Danielle E. Arnold, Danielle E. Arnold Immune Deficiency–Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD; https://orcid.org/0000-0001-7501-806X Search for other works by this author on: This Site PubMed Google Scholar Cristina Mecucci, Cristina Mecucci Department of Medicine, Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy; https://orcid.org/0000-0002-1623-0148 Search for other works by this author on: This Site PubMed Google Scholar Siobán B. Keel, Siobán B. Keel Department of Medicine, Division of Hematology, University of Washington, Seattle, WA; Search for other works by this author on: This Site PubMed Google Scholar Alison A. Bertuch, Alison A. Bertuch Department of Pediatrics/Hematology-Oncology, Baylor College of Medicine, Houston, TX; Search for other works by this author on: This Site PubMed Google Scholar Kiran Tawana, Kiran Tawana Department of Haematology, Addenbrooke's Hospital, Cambridge, United Kingdom; Search for other works by this author on: This Site PubMed Google Scholar Shlomit Barzilai, Shlomit Barzilai Pediatric Hematology and Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel;Sackler Faculty of Medicine, Tel Aviv University, Israel; Search for other works by this author on: This Site PubMed Google Scholar Shinsuke Hirabayashi, Shinsuke Hirabayashi Department of Pediatrics and https://orcid.org/0000-0001-7961-0968 Search for other works by this author on: This Site PubMed Google Scholar Masahiro Onozawa, Masahiro Onozawa Department of Hematology, Hokkaido University Faculty of Medicine, Graduate School of Medicine, Sapporo, Japan; https://orcid.org/0000-0001-9267-2864 Search for other works by this author on: This Site PubMed Google Scholar Shaohua Lei, Shaohua Lei Department of Computational Biology, St Jude Children's Research Hospital, Memphis, TN; Search for other works by this author on: This Site PubMed Google Scholar Helena Alaiz, Helena Alaiz Hematology Department, Oncology Institute Francisco Gentil, Lisbon, Portugal; Search for other works by this author on: This Site PubMed Google Scholar Hajnalka Andrikovics, Hajnalka Andrikovics Laboratory of Molecular Diagnostics, Central Hospital of Southern Pest, Budapest, Hungary; Search for other works by this author on: This Site PubMed Google Scholar David Betts, David Betts National Children's Cancer Service, Children's Health Ireland at Crumlin, Dublin, Ireland; Search for other works by this author on: This Site PubMed Google Scholar Berna H. Beverloo, Berna H. Beverloo Dutch Childhood Oncology Group (DCOG), Utrecht, The Netherlands;Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Search for other works by this author on: This Site PubMed Google Scholar Jochen Buechner, Jochen Buechner Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway; https://orcid.org/0000-0001-5848-4501 Search for other works by this author on: This Site PubMed Google Scholar Martin Čermák, Martin Čermák Department of Genetics, The National Institute of Oncology, Bratislava, Slovakia; https://orcid.org/0000-0002-9949-0163 Search for other works by this author on: This Site PubMed Google Scholar José Cervera, José Cervera Department of Hematology, Genetics Unit, Centro de Investigación Biomédica en Red de Oncología (CIBERONC), Hospital Universitario y Politécnico La Fe, Valencia, Spain; Search for other works by this author on: This Site PubMed Google Scholar Olga Haus, Olga Haus Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland; Search for other works by this author on: This Site PubMed Google Scholar Kirsi Jahnukainen, Kirsi Jahnukainen New Children's Hospital, Pediatric Research Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;Department of Women's and Children's Health, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Search for other works by this author on: This Site PubMed Google Scholar Kalliopi N. Manola, Kalliopi N. Manola Department of Biodiagnostic Sciences and Technologies, The Institute of Nuclear & Radiological Sciences and Technology, Energy & Safety (INRASTES), National Centre for Research 'Demokritos', Athens, Greece; Search for other works by this author on: This Site PubMed Google Scholar Karin Nebral, Karin Nebral Labdia Labordiagnostik GmbH, Clinical Genetics, Vienna, Austria; https://orcid.org/0000-0002-0548-541X Search for other works by this author on: This Site PubMed Google Scholar Francesco Pasquali, Francesco Pasquali Medical Genetics, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Search for other works by this author on: This Site PubMed Google Scholar Joelle Tchinda, Joelle Tchinda Laboratory for Oncology, University Children's Hospital Zürich, Zürich, Switzerland; Search for other works by this author on: This Site PubMed Google Scholar Dominik Turkiewicz, Dominik Turkiewicz Department of Pediatrics, Section of Pediatric Oncology, Hematology, Immunology and Nephrology, Skåne University Hospital, Lund, Sweden; Search for other works by this author on: This Site PubMed Google Scholar Nadine Van Roy, Nadine Van Roy Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Search for other works by this author on: This Site PubMed Google Scholar Zuzana Zemanova, Zuzana Zemanova Center of Oncocytogenomics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, Prague, Czech Republic; and Search for other works by this author on: This Site PubMed Google Scholar Victor B. Pastor, Victor B. Pastor Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, and Search for other works by this author on: This Site PubMed Google Scholar Brigitte Strahm, Brigitte Strahm Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, and https://orcid.org/0000-0002-6086-130X Search for other works by this author on: This Site PubMed Google Scholar Peter Noellke, Peter Noellke Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, and https://orcid.org/0000-0002-0281-4732 Search for other works by this author on: This Site PubMed Google Scholar Charlotte M. Niemeyer, Charlotte M. Niemeyer Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, andGerman Cancer Consortium (DKTK), Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany https://orcid.org/0000-0003-3856-7937 Search for other works by this author on: This Site PubMed Google Scholar Brigitte Schlegelberger, Brigitte Schlegelberger Department of Human Genetics, Hannover Medical School, Hannover, Germany; https://orcid.org/0000-0001-5256-1270 Search for other works by this author on: This Site PubMed Google Scholar Ayami Yoshimi, Ayami Yoshimi Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, and Search for other works by this author on: This Site PubMed Google Scholar Marcin W. Wlodarski Marcin W. Wlodarski Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, andDepartment of Hematology, St Jude Children's Research Hospital, Memphis, TN; https://orcid.org/0000-0001-6638-9643 Search for other works by this author on: This Site PubMed Google Scholar Blood (2021) 138 (23): 2441–2445. https://doi.org/10.1182/blood.2021012781 Article history Submitted: June 4, 2021 Accepted: August 5, 2021 First Edition: September 1, 2021 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Emilia J. Kozyra, Gudrun Göhring, Dennis D. Hickstein, Katherine R. Calvo, Courtney D. DiNardo, Michael Dworzak, Valerie de Haas, Jan Starý, Henrik Hasle, Akiko Shimamura, Mark D. Fleming, Hiroto Inaba, Sara Lewis, Amy P. Hsu, Steven M. Holland, Danielle E. Arnold, Cristina Mecucci, Siobán B. Keel, Alison A. Bertuch, Kiran Tawana, Shlomit Barzilai, Shinsuke Hirabayashi, Masahiro Onozawa, Shaohua Lei, Helena Alaiz, Hajnalka Andrikovics, David Betts, Berna H. Beverloo, Jochen Buechner, Martin Čermák, José Cervera, Olga Haus, Kirsi Jahnukainen, Kalliopi N. Manola, Karin Nebral, Francesco Pasquali, Joelle Tchinda, Dominik Turkiewicz, Nadine Van Roy, Zuzana Zemanova, Victor B. Pastor, Brigitte Strahm, Peter Noellke, Charlotte M. Niemeyer, Brigitte Schlegelberger, Ayami Yoshimi, Marcin W. Wlodarski; Association of unbalanced translocation der(1;7) with germline GATA2 mutations. Blood 2021; 138 (23): 2441–2445. doi: https://doi.org/10.1182/blood.2021012781 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Myeloid Neoplasia TO THE EDITOR: GATA2 deficiency is an autosomal dominant disorder predisposing to myeloid neoplasia and immunodeficiency.1-4 GATA2-related myelodysplastic syndrome (MDS) may present early in life and is commonly associated with monosomy 7 and trisomy 8 karyotypes.5,6 Der(1;7)(q10;p10), henceforth der(1;7), is an unbalanced whole-arm chromosomal translocation resulting in trisomy 1q and deletion 7q (del(7q)) (Figure 1A).7 This translocation has been recurrently reported in adults with primary and therapy-related hematopoietic malignancies, whereas in children it is associated with primary MDS.6,8-10 Previously, we and others reported single cases of GATA2 deficiency that carry der(1;7).4,6,11–15 Building on this intriguing observation, we aimed to define the prevalence of der(1;7) in pediatric MDS according to germline GATA2 mutation (GATA2mut) status and describe the features of this unique subgroup. We evaluated 1620 children and adolescents with primary MDS consecutively enrolled in the registries of the European... REFERENCES 1.Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011;118(10):2653-2655.Google ScholarCrossrefSearch ADS PubMed 2.Dickinson RE, Griffin H, Bigley V, et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood. 2011;118(10):2656-2658.Google ScholarCrossrefSearch ADS PubMed 3.Hahn CN, Chong CE, Carmichael CL, et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011;43(10):1012-1017.Google ScholarCrossrefSearch ADS PubMed 4.Pasquet M, Bellanné-Chantelot C, Tavitian S, et al. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood. 2013;121(5):822-829.Google ScholarCrossrefSearch ADS PubMed 5.Nováková M, Žaliová M, Suková M, et al. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome. Haematologica. 2016;101(6): 707-716.Google ScholarCrossrefSearch ADS PubMed 6.Wlodarski MW, Hirabayashi S, Pastor V, et al; EWOG-MDS. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127(11):1387-1397, quiz 1518.Google ScholarCrossrefSearch ADS PubMed 7.Wang L, Ogawa S, Hangaishi A, et al. Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10). Blood. 2003;102(7):2597-2604.Google ScholarCrossrefSearch ADS PubMed 8.Hussain FT, Nguyen EP, Raza S, et al. Sole abnormalities of chromosome 7 in myeloid malignancies: spectrum, histopathologic correlates, and prognostic implications. Am J Hematol. 2012;87(7):684-686.Google ScholarCrossrefSearch ADS PubMed 9.Ganster C, Müller-Thomas C, Haferlach C, et al. Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes. Genes Chromosomes Cancer. 2019;58(10):689-697.Google ScholarCrossrefSearch ADS PubMed 10.Göhring G, Michalova K, Beverloo HB, et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766-3769.Google ScholarCrossrefSearch ADS PubMed 11.Ganapathi KA, Townsley DM, Hsu AP, et al. GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. Blood. 2015;125(1):56-70.Google ScholarCrossrefSearch ADS PubMed 12.Wang X, Muramatsu H, Okuno Y, et al. GATA2 and secondary mutations in familial myelodysplastic syndromes and pediatric myeloid malignancies. Haematologica. 2015;100(10):e398-e401.Google ScholarCrossrefSearch ADS PubMed 13.Schwartz JR, Ma J, Lamprecht T, et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8(1):1557.Google ScholarCrossrefSearch ADS PubMed 14.Kurata T, Shigemura T, Muramatsu H, Okuno Y, Nakazawa Y. A case of GATA2-related myelodysplastic syndrome with unbalanced translocation der(1;7)(q10;p10). Pediatr Blood Cancer. 2017;64(8): e26419.Google ScholarCrossrefSearch ADS 15.Donadieu J, Lamant M, Fieschi C, et al; French GATA2 study group. Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. Haematologica. 2018;103(8):1278-1287.Google ScholarCrossrefSearch ADS PubMed 16.Pozdnyakova O, Miron PM, Tang G, et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer. 2008;113(12):3331-3340.Google ScholarCrossrefSearch ADS PubMed 17.Zhang T, Xu Y, Pan J, et al. High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10). Leukemia. 2017;31(10):2257-2260.Google ScholarCrossrefSearch ADS PubMed 18.Wlodarski MW, Collin M, Horwitz MS. GATA2 deficiency and related myeloid neoplasms. Semin Hematol. 2017;54(2):81-86.Google ScholarCrossrefSearch ADS PubMed 19.Wehr C, Grotius K, Casadei S, et al. A novel disease-causing synonymous exonic mutation in GATA2 affecting RNA splicing. Blood. 2018;132(11):1211-1215.Google ScholarCrossrefSearch ADS PubMed 20.Kozyra EJ, Pastor VB, Lefkopoulos S, et al; European Working Group of MDS in Childhood (EWOG-MDS). Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency. Leukemia. 2020;34(10):2673-2687.Google ScholarCrossrefSearch ADS PubMed 21.Fox LC, Tan M, Brown AL, et al. A synonymous GATA2 variant underlying familial myeloid malignancy with striking intrafamilial phenotypic variability. Br J Haematol. 2020;190(5):e297-e301.Google ScholarCrossrefSearch ADS PubMed 22.Gao J, Gentzler RD, Timms AE, et al. Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature [published correction appears in J Hematol Oncol. 2015;8:131]. J Hematol Oncol. 2014;7(1):36.Google ScholarCrossrefSearch ADS PubMed 23.Hahn CN, Brautigan PJ, Chong CE, et al. Characterisation of a compound in-cis GATA2 germline mutation in a pedigree presenting with myelodysplastic syndrome/acute myeloid leukemia with concurrent thrombocytopenia. Leukemia. 2015;29(8):1795-1797.Google ScholarCrossrefSearch ADS PubMed 24.Catto LFB, Borges G, Pinto AL, et al. Somatic genetic rescue in hematopoietic cells in GATA2 deficiency. Blood. 2020;136(8):1002-1005.Google ScholarCrossrefSearch ADS PubMed 25.Pastor V, Hirabayashi S, Karow A, et al. Mutational landscape in children with myelodysplastic syndromes is distinct from adults: specific somatic drivers and novel germline variants. Leukemia. 2017;31(3):759-762.Google ScholarCrossrefSearch ADS PubMed 26.Pastor VB, Sahoo SS, Boklan J, et al. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica. 2018;103(3):427-437.Google ScholarCrossrefSearch ADS PubMed 27.Fernandez AGL, Crescenzi B, Pierini V, et al. A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes. Leukemia. 2019;33(10):2481-2494.Google ScholarCrossrefSearch ADS PubMed You do not currently have access to this content. 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