medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-253medsovet-10344Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONКлинический случай миелодиспластического синдрома с моносомией 7 у пациента с мутацией в гене SAMD9LA clinical case of myelodysplastic syndrome with monosomy 7 in a patient with a mutation in the SAMD9L genehttps://orcid.org/0000-0003-1450-8254РашитоваЭ. Л.RashitovaE. L.

Рашитова Элина Ленаровна, врач-ординатор (гематология)

117198, Москва, ул. Саморы Машела, д. 1

Elina L. Rashitova, Resident Physician in Hematology

1, Samora Mashel St., Moscow, 117198

elina.rashitova@gmail.comhttps://orcid.org/0000-0001-9533-6583БанколеВ. А.BankoleV. A.

Банколе Ванесса Адетунджиновна, врач-гематолог отделения детской гематологии/онкологии

117198, Москва, ул. Саморы Машела, д. 1

Vanessa A. Bankole, Hematologist of the Department of Pediatric Hematology/Oncology 

1, Samora Mashel St., Moscow, 117198

vanessa.bankole@dgoi.ruhttps://orcid.org/0000-0001-7130-8596БайдильдинаД. Д.BaydildinaD. D.

Байдильдина Дина Дамировна, к.м.н., врач-гематолог, заместитель заведующего отделением детской гематологии/онкологии

117198, Москва, ул. Саморы Машела, д. 1

Dina D. Baydildina, Cand. Sci. (Med.), Hematologist, Deputy Head of the Department of Pediatric Hematology/Oncology 

1, Samora Mashel St., Moscow, 117198

DinaBaydildina@dgoi.ruНациональный медицинский исследовательский центр детской гематологии, онкологии и иммунологии имени Дмитрия РогачеваРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and ImmunologyRussian Federation202607092026010159165Copyright © Рашитова Э.Л., Банколе В.А., Байдильдина Д.Д., 20262026Рашитова Э.Л., Банколе В.А., Байдильдина Д.Д.Rashitova E.L., Bankole V.A., Baydildina D.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/10344

Состояния, ассоциированные с дефектами в генах SAMD9 и SAMD9L, – это группа нозологий со спектром клинических симптомов от мультисистемного поражения в рамках синдрома MIRAGE до изолированных гематологических проявлений. В статье представлен клинический случай пациентки с миелодиспластическим синдромом и герминальной мутацией в гене SAMD9L. Пациентка В. заболела остро в возрасте 1 года 1 мес. Госпитализирована с жалобами на геморрагическую сыпь, повышение температуры тела; в гемограмме – изолированная тромбоцитопения. Установлен диагноз «иммунная тромбоцитопения». Учитывая отсутствие эффекта от 1-й линии терапии, диагноз пересмотрен на «апластическая анемия». Через 8 дней – спонтанное восстановление гемопоэза. В возрасте 1 года 5 мес. отмечались тромбоцитопения, нейтропения. В возрасте 2 лет первично госпитализирована в НМИЦ ДГОИ им. Д. Рогачева, где был установлен диагноз «миелодиспластический синдром, моносомия 7-й хромосомы». Единственным куративным методом лечения заболевания является аллогенная трансплантация гемопоэтических стволовых клеток (ТГСК). По результатам полногеномного секвенирования обнаружена герминальная de novo миссенс-мутация в гене SAMD9L (gain-of-function). В 2 года 10 мес. – повторная госпитализация в НМИЦ ДГОИ им. Д. Рогачева: исключена трансформация в острый лейкоз и выполнена аллогенная ТГСК от родственного гаплоидентичного донора. При контрольном обследовании в рамках +30-х сут. трансплантат функционирует удовлетворительно, в миелограмме бласты менее 5%, признаков диспоэза не выявлено. Состояния, связанные с мутациями в генах SAMD9/SAMD9L, встречаются редко. Своевременная диагностика и оперативное проведение ТГСК позволяют улучшить показатели выживаемости и снизить риск долгосрочных осложнений.

Conditions associated with defects in the SAMD9 and SAMD9L genes are a group of nosologies with a range of clinical symptoms from multisystem lesions in the framework of MIRAGE syndrome to isolated hematological manifestations. The article presents a clinical case of a patient with myelodysplastic syndrome and a germline mutation in the SAMD9L gene. Patient V. developed first symptoms of her illness at the age of 1 year 1 month. She was hospitalized with complaints of a hemorrhagic rash and fever; the hemogram showed isolated thrombocytopenia. A diagnosis of immune thrombocytopenia was established. Given the lack of effect from the first-line therapy, the diagnosis was revised to aplastic anemia. Spontaneous restoration of hematopoiesis was observed 8 days later. At the age of 1 year 5 months, thrombocytopenia and neutropenia were observed. At the age of 2 years, she was initially hospitalized at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and was diagnosed with myelodysplastic syndrome, monosomy 7. The only curative treatment for the disease is allogeneic hematopoietic stem cell transplantation (HSCT). Based on the results of wholegenome sequencing, a germline de novo missense mutation in the SAMD9L gene (“gain-of-function”) was detected. At 2 years and 10 months, the patient was readmitted to the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Transformation into acute leukemia was ruled out, and allogeneic HSCT was performed from a related haploidentical donor. A follow-up examination within the 30th day showed that the graft was functioning satisfactorily, with blasts less than 5% in the myelogram and no signs of dyspoiesis. Conditions associated with mutations in the SAMD9/SAMD9L genes are rare. Timely diagnosis and prompt HSCT can improve survival rates and reduce the risk of long-term complications.

миелодиспластический синдром у детеймоносомия 7-й хромосомымутации в генах SAMD9/SAMD9Lтрансплантациягемопоэтические стволовые клеткиmyelodysplastic syndrome in childrenchromosome 7 monosomymutations in the SAMD9/SAMD9L genestransplantationhematopoietic stem cellsReferencesHasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia. 1995;9(9):1569–1572. Available at: https://pubmed.ncbi.nlm.nih.gov/7658725/.Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia. 1995;9(9):1569–1572. Available at: https://pubmed.ncbi.nlm.nih.gov/7658725/.Passmore SJ, Chessells JM, Kempski H, Hann IM, Brownbill PA, Stiller CA. Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival. Br J Haematol. 2003;121(5):758–767. https://doi.org/10.1046/j.1365-2141.2003.04361.x.Passmore SJ, Chessells JM, Kempski H, Hann IM, Brownbill PA, Stiller CA. Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival. Br J Haematol. 2003;121(5):758–767. https://doi.org/10.1046/j.1365-2141.2003.04361.x.Jackson GH, Carey PJ, Cant AJ, Bown NP, Reid MM. Myelodysplastic syndromes in children. Br J Haematol. 1993;84(1):185–186. https://doi.org/10.1111/j.1365-2141.1993.tb03049.x.Jackson GH, Carey PJ, Cant AJ, Bown NP, Reid MM. Myelodysplastic syndromes in children. Br J Haematol. 1993;84(1):185–186. https://doi.org/10.1111/j.1365-2141.1993.tb03049.x.Williamson PJ, Kruger AR, Reynolds PJ, Hamblin TJ, Oscier DG. Establishing the incidence of myelodysplastic syndrome. Br J Haematol. 1994;87(4):743–745. https://doi.org/10.1111/j.1365-2141.1994.tb06733.x.Williamson PJ, Kruger AR, Reynolds PJ, Hamblin TJ, Oscier DG. Establishing the incidence of myelodysplastic syndrome. Br J Haematol. 1994;87(4):743–745. https://doi.org/10.1111/j.1365-2141.1994.tb06733.x.Alter BP, Giri N, Savage SA, Peters JA, Loud JT, Leathwood L et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol. 2010;150(2):179–188. https://doi.org/10.1111/j.1365-2141.2010.08212.x.Alter BP, Giri N, Savage SA, Peters JA, Loud JT, Leathwood L et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol. 2010;150(2):179–188. https://doi.org/10.1111/j.1365-2141.2010.08212.x.Göhring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766–3769. https://doi.org/10.1182/blood-2010-04-280313.Göhring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA et al. Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 2010;116(19):3766–3769. https://doi.org/10.1182/blood-2010-04-280313.Hasle H, Clausen N, Pedersen B, Bendix-Hansen K. Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype. Cancer Genet Cytogenet. 1995;79(1):79–81. https://doi.org/10.1016/0165-4608(94)00099-w.Hasle H, Clausen N, Pedersen B, Bendix-Hansen K. Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype. Cancer Genet Cytogenet. 1995;79(1):79–81. https://doi.org/10.1016/ 0165-4608(94)00099-w.Boultwood J, Lewis S, Wainscoat JS. The 5q-syndrome. Blood. 1994;84(10):3253–3260. https://doi.org/10.1182/blood.V84.10.3253.3253.Boultwood J, Lewis S, Wainscoat JS. The 5q-syndrome. Blood. 1994;84(10):3253–3260. https://doi.org/10.1182/blood.V84.10.3253.3253.Veltroni M, Sainati L, Zecca M, Fenu S, Tridello G, Testi AM et al. Advanced pediatric myelodysplastic syndromes: can immunophenotypic characterization of blast cells be a diagnostic and prognostic tool? Pediatr Blood Cancer. 2009;52(3):357–363. https://doi.org/10.1002/pbc.21874.Veltroni M, Sainati L, Zecca M, Fenu S, Tridello G, Testi AM et al. Advanced pediatric myelodysplastic syndromes: can immunophenotypic characterization of blast cells be a diagnostic and prognostic tool? Pediatr Blood Cancer. 2009;52(3):357–363. https://doi.org/10.1002/pbc.21874.Castro-Malaspina H, Harris RE, Gajewski J, Ramsay N, Collins R, Dharan B et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood. 2002;99(6):1943–1951. https://doi.org/10.1182/blood.v99.6.1943.Castro-Malaspina H, Harris RE, Gajewski J, Ramsay N, Collins R, Dharan B et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood. 2002;99(6):1943–1951. https://doi.org/10.1182/blood.v99.6.1943.Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25(3):455–462. https://doi.org/10.1038/leu.2010.297.Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25(3):455–462. https://doi.org/10.1038/leu.2010.297.Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood. 2003;102(6):1997–2003. https://doi.org/10.1182/blood-2002-11-3444.Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood. 2003;102(6):1997–2003. https://doi.org/10.1182/blood-2002-11-3444.Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109(11):4641–4647. https://doi.org/10.1182/blood-2006-10-051342.Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109(11):4641–4647. https://doi.org/10.1182/blood-2006-10-051342.Aktas D, Koc A, Boduroğlu K, Hicsonmez G, Tuncbilek E. Myelodysplastic Syndrome Associated with Monosomy 7 in a Child with Bloom Syndrome. Cancer Genet Cytogenet. 2000;116(1):44–46. https://doi.org/10.1016/S0165-4608(99)00099-0.Aktas D, Koc A, Boduroğlu K, Hicsonmez G, Tuncbilek E. Myelodysplastic Syndrome Associated with Monosomy 7 in a Child with Bloom Syndrome. Cancer Genet Cytogenet. 2000;116(1):44–46. https://doi.org/10.1016/S0165-4608(99)00099-0.Porwit A, Saft L. The AML–MDS interface – leukemic transformation in myelodysplastic syndromes. J Hematopathol. 2011;4:69–79. Available at: https://link.springer.com/article/10.1007/s12308-011-0088-6.Porwit A, Saft L. The AML–MDS interface – leukemic transformation in myelodysplastic syndromes. J Hematopathol. 2011;4:69–79. Available at: https://link.springer.com/article/10.1007/s12308-011-0088-6.Schwartz JR, Ma J, Lamprecht T, Walsh M, Wang S, Bryant V et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8(1):1557. https://doi.org/10.1038/s41467-017-01590-5.Schwartz JR, Ma J, Lamprecht T, Walsh M, Wang S, Bryant V et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat Commun. 2017;8(1):1557. https://doi.org/10.1038/s41467-017-01590-5.Sahoo S, Pastor V, Goodings Ch, Voss R, Kozyra E, Szvetnik A et al. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nat Med. 2021;27(10):1806–1817. https://doi.org/10.1038/s41591-021-01511-6.Sahoo S, Pastor V, Goodings Ch, Voss R, Kozyra E, Szvetnik A et al. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nat Med. 2021;27(10):1806–1817. https://doi.org/10.1038/s41591-021-01511-6.Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66–81. https://doi.org/10.1007/s10875-020-00758-x.Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol. 2020;40(1):66–81. https://doi.org/10.1007/s10875-020-00758-x.Аведова АЯ, Мерсиянова ИВ, Павлова АВ, Султанова ЭР, Петрова УН, Балашов ДН и др. Клиническая характеристика пациентов с дефектами генов SAMD9/SAMD9L. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022;21(3):126–135. https://doi.org/10.24287/1726-1708-2022-21-3-126-135.Avedova AYa, Mersiyanova IV, Pavlova AV, Sultanova ER, Petrova UN, Balashov DN et al. Clinical characteristics of patients with SAMD9/SAMD9L gene defects. Pediatric Hematology/Oncology and Immunopathology. 2022;21(3):126–135. (In Russ.) https://doi.org/10.24287/1726-1708-2022-21-3-126-135.Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M et al. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat Genet. 2016;48(7):792–797. https://doi.org/10.1038/ng.3569.Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M et al. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat Genet. 2016;48(7):792–797. https://doi.org/10.1038/ng.3569.Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Kanai A et al. Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7. Cancer Cell. 2013;24(3):305–317. https://doi.org/10.1016/j.ccr.2013.08.011.Nagamachi A, Matsui H, Asou H, Ozaki Y, Aki D, Kanai A et al. Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7. Cancer Cell. 2013;24(3):305–317. https://doi.org/10.1016/j.ccr.2013.08.011.Buonocore F, Kühnen P, Suntharalingham JP, Del Valle I, Digweed M, Stachelscheid H et al. Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans. J Clin Invest. 2017;127(5):1700–1713. https://doi.org/10.1172/JCI91913.Buonocore F, Kühnen P, Suntharalingham JP, Del Valle I, Digweed M, Stachelscheid H et al. Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans. J Clin Invest. 2017;127(5):1700–1713. https://doi.org/10.1172/JCI91913.Nagata Y, Narumi S, Guan Y, Przychodzen B, Hirsch C, Makishima H et al. Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes. Blood. 2018;132(21):2309–2313. https://doi.org/10.1182/blood-2017-05-787390.Nagata Y, Narumi S, Guan Y, Przychodzen B, Hirsch C, Makishima H et al. Germline loss-of-function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes. Blood. 2018;132(21):2309–2313. https://doi.org/10.1182/blood-2017-05-787390.Russell AJ, Gray PE, Ziegler JB, Kim YJ, Smith S, Sewell WA et al. SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cellautonomous translational repression. Proc Natl Acad Sci U S A. 2021;118(34):e2110190118. https://doi.org/10.1073/pnas.2110190118.Russell AJ, Gray PE, Ziegler JB, Kim YJ, Smith S, Sewell WA et al. SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cellautonomous translational repression. Proc Natl Acad Sci U S A. 2021;118(34):e2110190118. https://doi.org/10.1073/pnas.2110190118.Allenspach EJ, Soveg F, Finn LS, So L, Gorman JA, Rosen ABI et al. Germline SAMD9L truncation variants trigger global translational repression. J Exp Med. 2021;218(5):e20201195. https://doi.org/10.1084/jem.20201195.Allenspach EJ, Soveg F, Finn LS, So L, Gorman JA, Rosen ABI et al. Germline SAMD9L truncation variants trigger global translational repression. J Exp Med. 2021;218(5):e20201195. https://doi.org/10.1084/jem.20201195.Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E et al. A land-scape of germ line mutations in a cohort of inherited bone marrow failure patients. Blood. 2018;131(7):717–732. https://doi.org/10.1182/blood-2017-09-806489.Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E et al. A land-scape of germ line mutations in a cohort of inherited bone marrow failure patients. Blood. 2018;131(7):717–732. https://doi.org/10.1182/blood-2017-09-806489.Sahoo SS, Kozyra EJ, Wlodarski MW. Germline predisposition in myeloid neo-plasms: Unique genetic and clinical fea-tures of GATA2 deficiency and SAMD9/SAMD9L syndromes. Best Pract Res Clin Haematol. 2020;33(3):101197. https://doi.org/10.1016/j.beha.2020.101197.Sahoo SS, Kozyra EJ, Wlodarski MW. Germline predisposition in myeloid neo-plasms: Unique genetic and clinical fea-tures of GATA2 deficiency and SAMD9/SAMD9L syndromes. Best Pract Res Clin Haematol. 2020;33(3):101197. https://doi.org/10.1016/j.beha.2020.101197.Chen DH, Below J, Shimamura A, Keel S, Matsushita M, Wolff J et al. AtaxiaAtaxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. Am J Hum Genet. 2016;98(6):1146–1158. https://doi.org/10.1016/j.ajhg.2016.04.009.Chen DH, Below J, Shimamura A, Keel S, Matsushita M, Wolff J et al. AtaxiaAtaxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. Am J Hum Genet. 2016;98(6):1146–1158. https://doi.org/10.1016/j.ajhg.2016.04.009.Tesi B, Davidsson J, Voss M, Rahikkala E, Holmes TD, Chiang SCC et al. Gainof-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood. 2017;129(16):2266–2279. https://doi.org/10.1182/blood-2016-10-743302.Tesi B, Davidsson J, Voss M, Rahikkala E, Holmes TD, Chiang SCC et al. Gainof-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood. 2017;129(16):2266–2279. https://doi.org/10.1182/blood-2016-10-743302.De Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y et al. Distinct interferon signatures and cytokine pat-terns define additional systemic autoin-flammatory diseases. J Clin Invest. 2020;130(4):1669–1682. https://doi.org/10.1172/JCI129301.De Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y et al. Distinct interferon signatures and cytokine pat-terns define additional systemic autoin-flammatory diseases. J Clin Invest. 2020;130(4):1669–1682. https://doi.org/10.1172/JCI129301.Duncan AW, Newell A, Bi W, Finegold M, Olson S, Beaudet A et al. Aneuploidy as a mechanism for stress-induced liver adaptation. J Clin Invest. 2012;122(9):3307–3315. https://doi.org/10.1172/JCI64026.Duncan AW, Newell A, Bi W, Finegold M, Olson S, Beaudet A et al. Aneuploidy as a mechanism for stress-induced liver adaptation. J Clin Invest. 2012;122(9):3307–3315. https://doi.org/10.1172/JCI64026.Davidsson J, Puschmann A, Tedgård U, Bryder D, Nilsson L, Cammenga J. SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies. Leukemia. 2018;32(5):1106–1115. https://doi.org/10.1038/s41375-018-0074-4.Davidsson J, Puschmann A, Tedgård U, Bryder D, Nilsson L, Cammenga J. SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies. Leukemia. 2018;32(5):1106–1115. https://doi.org/10.1038/s41375-018-0074-4.Thomas ME 3rd, Abdelhamed S, Hiltenbrand R, Schwartz JR, Sakurada SM, Walsh M et al. Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hemato-poietic cells. Leukemia. 2021;35(11):3232–3244. https://doi.org/10.1038/s41375-021-01212-6.Thomas ME 3rd, Abdelhamed S, Hiltenbrand R, Schwartz JR, Sakurada SM, Walsh M et al. Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hemato-poietic cells. Leukemia. 2021;35(11):3232–3244. https://doi.org/10.1038/s41375-021-01212-6.Sahoo SS, Pastor Loyola V, Panda PK, Szvetnik EA, Kozyra EJ, Voss RK et al. SAMD9 and SAMD9L germline disorders in patients enrolled in studies of the European working group of MDS in childhood (EWOG-MDS): prevalence, outcome, phenotype and functional characterisation. Blood. 2018;132(1):643. https://doi.org/10.1182/blood-2018-99-118389.Sahoo SS, Pastor Loyola V, Panda PK, Szvetnik EA, Kozyra EJ, Voss RK et al. SAMD9 and SAMD9L germline disorders in patients enrolled in studies of the European working group of MDS in childhood (EWOG-MDS): prevalence, outcome, phenotype and functional characterisation. Blood. 2018;132(1):643. https://doi.org/10.1182/blood-2018-99-118389.Ahmed IA, Farooqi MS, Vander Lugt MT, Boklan J, Rose M, Friehling ED et al. Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations. Biol Blood Marrow Transplant. 2019;25(11):2186–2196. https://doi.org/10.1016/j.bbmt.2019.07.007.Ahmed IA, Farooqi MS, Vander Lugt MT, Boklan J, Rose M, Friehling ED et al. Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations. Biol Blood Marrow Transplant. 2019;25(11):2186–2196. https://doi.org/10.1016/j.bbmt.2019.07.007.

The authors declare that there are no conflicts of interest present.