{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:47:20Z","timestamp":1777355240021,"version":"3.51.4"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUBZ.C200.22.067"],"award-info":[{"award-number":["SUBZ.C200.22.067"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>GATA-binding protein 2 (<jats:italic>GATA2<\/jats:italic>) is a transcription factor responsible for the regulation of blood cell proliferation, differentiation, and maintenance in hematopoietic stem cells. Here, we describe successful bone marrow transplantation in a carrier of a novel GATA2 pathogenic variant who was diagnosed with immunodeficiency a few years after completion of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. At the age of 4 years, the patient was diagnosed with and treated for BCP-ALL. Antileukemic therapy was complicated by pulmonary cryptococcosis. Two years after completion of the maintenance therapy, the child was consulted by an immunologist because of recurrent respiratory tract infections and an episode of sepsis. Flow cytometry revealed deep monocytopenia, lymphopenia, absence of B lymphocytes, considerably reduced NK cells, poor thymic T lymphocyte production, minor defects in T cell maturation, and absence of TCR\u03b3\u03b4+ T cells. The presence of the likely pathogenic, heterozygous missense variant within exon 5 of <jats:italic>GATA2<\/jats:italic> (NM_032638.5: c.1047T&amp;gt;G, Cys349Trp) was identified in the proband and confirmed in the father of the patient, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor due to myelodysplastic syndrome with excess blasts at the age of 22 years. An allogeneic hematopoietic stem cell transplantation with a reduced toxicity conditioning protocol was performed using a matched sibling donor. Pre-transplant conditioning included fludarabine (5 \u00d7 30 mg\/m2), treosulfan (3 \u00d7 14 g\/m2), and thiotepa (10 mg\/kg). Complete donor chimerism was achieved on post-transplant day 17. During the 12 months of the posttransplant observation period, she remained free from symptoms of acute or chronic graft-versus-host disease, and immunosuppressive treatment was therefore stopped. This is the second reported case of BCP-ALL in a patient with <jats:italic>GATA2<\/jats:italic> deficiency, and the first successfully treated with a reduced-toxicity conditioning HSCT protocol. The co-occurrence of lymphoid malignancies and primary immunodeficiencies points to the role of genetic counseling and family screening for possible cancer predisposition syndromes prior to the selection of related HSCT donors.<\/jats:p>","DOI":"10.3389\/fimmu.2022.928529","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T05:14:45Z","timestamp":1659417285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Edyta","family":"Heropolita\u0144ska-Pliszka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Pi\u0105tosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Szmydki-Baran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Kuczborska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Miarka-Walczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Pastorczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ukasz","family":"S\u0119dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Szczepa\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Ussowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.10.3636","article-title":"Transcription factor GATA-2 is required for proliferation\/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation","volume":"89","author":"Tsai","year":"1997","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.3.575.575","article-title":"GATA-binding transcription factors in hematopoietic cells","volume":"80","author":"Orkin","year":"1992","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ng.913","article-title":"Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia","volume":"43","author":"Hahn","year":"2011","journal-title":"Nat Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-356352","article-title":"Mutations in GATA2 a re associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome","volume":"118","author":"Hsu","year":"2011","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-517151","article-title":"The evolution of cellular deficiency in GATA2 mutation","volume":"123","author":"Dickinson","year":"2014","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.384","article-title":"Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA 2 mutations","volume":"4","author":"Mir","year":"2015","journal-title":"Cancer Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00092910","article-title":"Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan","volume":"37","author":"Ishii","year":"2011","journal-title":"Eur Respir J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-515528","article-title":"GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity","volume":"123","author":"Spinner","year":"2014","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27649","article-title":"A unique phenotype of T-cell acute lymphoblastic leukemia in a patient with GATA2 haploinsufficiency","volume":"66","author":"Esparza","year":"2019","journal-title":"Pediatr Blood Cancer."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26084","article-title":"Acute lymphoblastic leukemia in a patient with MonoMAC syndrome\/GATA2 haploinsufficiency","volume":"63","author":"Koegel","year":"2016","journal-title":"Pediatr Blood Cancer."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.120","article-title":"EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes","volume":"26","author":"van Dongen","year":"2012","journal-title":"Leukemia"},{"key":"B12","unstructured":"ALL IC-BFM 2009 a randomized trial of the I-BFM-SG for the management of childhood non-b acute lymphoblastic leukemia. final version of therapy protocol from august-14-20092009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.181909","article-title":"Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients","volume":"103","author":"Donadieu","year":"2018","journal-title":"Haematologica"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0899-5","article-title":"Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency","volume":"34","author":"Kozyra","year":"2020","journal-title":"Leukemia"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-669937","article-title":"Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents","volume":"127","author":"Wlodarski","year":"2016","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-017-3076-9","article-title":"GATA2 gene analysis in several forms of hematological malignancies including familial aggregations","volume":"96","author":"Hamadou","year":"2017","journal-title":"Ann Hematol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13317","article-title":"Haematopoietic and immune defects associated with GATA2 mutation","volume":"169","author":"Collin","year":"2015","journal-title":"Br J Haematol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.795529","article-title":"Aberrant GATA2 activation in pediatric b-cell acute lymphoblastic leukemia","volume":"9","author":"Wang","year":"2022","journal-title":"Front Pediatr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2017.05.002","article-title":"GATA2 deficiency and related myeloid neoplasms","volume":"54","author":"Wlodarski","year":"2017","journal-title":"Semin Hematol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.14785\/lpsn-2014-0022","article-title":"Monocytosis in a patient with a novel GATA2 mutation","volume":"2","author":"Cada","year":"2015","journal-title":"LymphoSign J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.137711","article-title":"Loss of b cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome","volume":"101","author":"Novakova","year":"2016","journal-title":"Haematologica"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01189-y","article-title":"A nationwide study of GATA2 deficiency in Norway\u2013the majority of patients have undergone allo-HSCT","volume":"42","author":"J\u00f8rgensen","year":"2022","journal-title":"J Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005538","article-title":"Somatic genetic rescue in hematopoietic cells in GATA2 deficiency","volume":"136","author":"Catto","year":"2020","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000321","article-title":"Nordic Guidelines for germline predisposition to myeloid neoplasms in adults: Recommendations for genetic diagnosis, clinical management and follow-up","volume":"3","author":"Baliakas","year":"2019","journal-title":"HemaSphere"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-021-01374-y","article-title":"Hematopoietic stem cell transplantation in children and adolescents with GATA2-related myelodysplastic syndrome","volume":"56","author":"Bortnick","year":"2021","journal-title":"Bone Marrow Transplant."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2020.02.015","article-title":"Comparison of outcomes of myeloablative allogeneic stem cell transplantation for pediatric patients with bone marrow failure, myelodysplastic syndrome and acute myeloid leukemia with and without germline GATA2 mutations","volume":"26","author":"Hofmann","year":"2020","journal-title":"Biol Blood Marrow Transplant."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17840","article-title":"Donor source and post-transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency","volume":"196","author":"Nichols-Vinueza","year":"2022","journal-title":"Br J Haematol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1358\/dot.2020.56.6.3135200","article-title":"Treosulfan in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation","volume":"56","author":"Ussowicz","year":"2020","journal-title":"Drugs Today"},{"key":"B29","unstructured":"ESID EBMT HSCT guidelines 20172017"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.05.005","article-title":"Gonadal function after busulfan compared with treosulfan in children and adolescents undergoing allogeneic hematopoietic stem cell transplant","volume":"25","author":"Faraci","year":"2019","journal-title":"Biol Blood Marrow Transplant."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.928529\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T05:14:50Z","timestamp":1659417290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.928529\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2022.928529"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.928529","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]},"article-number":"928529"}}