Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia

被引：15

作者：

Kubota, Yasuo ^{[1
]}

Zawit, Misam ^{[1
]}

Durrani, Jibran ^{[1
]}

Shen, Wenyi ^{[1
,2
]}

Bahaj, Waled ^{[1
]}

Kewan, Tariq ^{[1
]}

Ponvilawan, Ben ^{[1
]}

Mori, Minako ^{[1
]}

Meggendorfer, Manja ^{[3
]}

Gurnari, Carmelo ^{[1
,4
]}

LaFramboise, Thomas ^{[5
]}

Feurstein, Simone ^{[6
,7
,8
]}

Sekeres, Mikkael A. ^{[9
]}

Visconte, Valeria ^{[1
]}

Godley, Lucy A. ^{[6
,7
]}

Haferlach, Torsten ^{[3
]}

Maciejewski, Jaroslaw P. ^{[1
]}

机构：

[1] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA

[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Hematol, Nanjing, Peoples R China

[3] MLL Munich Leukemia Lab, Munich, Germany

[4] Univ Roma Tor Vergata, Dept Biomed & Prevent, Immunol Mol Med & Appl Biotechnol, Rome, Italy

[5] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA

[6] Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA

[7] Univ Chicago, Dept Human Genet, Sect Hematol Oncol, Chicago, IL 60637 USA

[8] Heidelberg Univ Hosp, Dept Internal Med, Sect Hematol Oncol & Rheumatol, Heidelberg, Germany

[9] Univ Miami, Sylvester Comprehens Canc Ctr, Div Hematol, Miami, FL USA

来源：

LEUKEMIA | 2022年 / 36卷 / 12期

关键词：

VARIANTS; CLASSIFICATION; MUTATIONS; GENOMICS; CANCER;

D O I：

10.1038/s41375-022-01729-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Broader genetic screening has led to the growing recognition of the role of germline variants associated with adult bone marrow failure (BMF) and myeloid neoplasia (MN) not exclusively in children and young adults. In this study, we applied a germline variant panel to 3008 adult BMF and MN cases to assess the importance of germline genetics and its impact on disease phenotype and prognosis. In our cohort, up to 9.7% of BMF and 5.3% of MN cases carried germline variants. Our cohort also included heterozygous carriers of recessive traits, suggesting they contribute to the risk of BMF and MN. By gene category, variants of Fanconi anemia gene family represented the highest-frequency category for both BMF and MN cases, found in 4.9% and 1.7% cases, respectively. In addition, about 1.4% of BMF and 0.19% of MN cases harbored multiple germline variants affecting often functionally related genes as compound heterozygous. The burden of germline variants in BMF and MN was clearly associated with acquisition of monosomy 7. While BMF cases carrying germline variants showed similar overall survival as compared to the wild-type (WT) cases, MN cases with germline variants experienced a significantly shorter overall survival as compared to WT cases.

引用

页码：2827 / 2834

页数：8

共 35 条

[1] Pathophysiologic and clinical implications of molecular profiles resultant from deletion 5q [J].

Adema, Vera ;

Palomo, Laura ;

Walter, Wencke ;

Mallo, Mar ;

Hutter, Stephan ;

La Framboise, Thomas ;

Arenillas, Leonor ;

Meggendorfer, Manja ;

Radivoyevitch, Tomas ;

Xicoy, Blanca ;

Pellagatti, Andrea ;

Haferlach, Claudia ;

Boultwood, Jacqueline ;

Kern, Wolfgang ;

Visconte, Valeria ;

Sekeres, Mikkael ;

Barnard, John ;

Haferlach, Torsten ;

Sole, Francesc ;

Maciejewski, Jaroslaw P. .

EBIOMEDICINE, 2022, 80

[2] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[3] The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [J].

Arber, Daniel A. ;

Orazi, Attilio ;

Hasserjian, Robert ;

Thiele, Jurgen ;

Borowitz, Michael J. ;

Le Beau, Michelle M. ;

Bloomfield, Clara D. ;

Cazzola, Mario ;

Vardiman, James W. .

BLOOD, 2016, 127 (20) :2391-2405

[4] K313dup is a recurrent CEBPA mutation in de novo acute myeloid leukemia (AML) [J].

Carnicer, Maria J. ;

Lasa, Adriana ;

Buschbeck, Marcus ;

Serrano, Elena ;

Carricondo, Maite ;

Brunet, Salut ;

Aventin, Anna ;

Sierra, Jorge ;

Di Croce, Luciano ;

Nomdedeu, Josep F. .

ANNALS OF HEMATOLOGY, 2008, 87 (10) :819-827

[5] Hereditary Predisposition to Acute Myeloid Leukemia in Older Adults [J].

Fenwarth, Laurene ;

Caulier, Alexis ;

Lachaier, Emma ;

Goursaud, Laure ;

Marceau-Renaut, Alice ;

Fournier, Elise ;

Lebon, Delphine ;

Boyer, Thomas ;

Berthon, Celine ;

Marolleau, Jean-Pierre ;

Preudhomme, Claude ;

Duployez, Nicolas .

HEMASPHERE, 2021, 5 (04)

[6] Germline predisposition to hematopoietic malignancies [J].

Feurstein, Simone ;

Drazer, Michael ;

Godley, Lucy A. .

HUMAN MOLECULAR GENETICS, 2021, 30 (R2) :R225-R235

[7] Germline variants drive myelodysplastic syndrome in young adults [J].

Feurstein, Simone ;

Churpek, Jane E. ;

Walsh, Tom ;

Keel, Sioban ;

Hakkarainen, Marja ;

Schroeder, Thomas ;

Germing, Ulrich ;

Geyh, Stefanie ;

Heuser, Michael ;

Thol, Felicitas ;

Pohlkamp, Christian ;

Haferlach, Torsten ;

Gao, Juehua ;

Owen, Carolyn ;

Goehring, Gudrun ;

Schlegelberger, Brigitte ;

Verma, Divij ;

Krause, Daniela S. ;

Gao, Guimin ;

Cronin, Tara ;

Gulsuner, Suleyman ;

Lee, Ming ;

Pritchard, Colin C. ;

Subramanian, Hari Prasanna ;

del Gaudio, Daniela ;

Li, Zejuan ;

Das, Soma ;

Kilpivaara, Outi ;

Wartiovaara-Kautto, Ulla ;

Wang, Eunice S. ;

Griffiths, Elizabeth A. ;

Dohner, Konstanze ;

Dohner, Hartmut ;

King, Mary-Claire ;

Godley, Lucy A. .

LEUKEMIA, 2021, 35 (08) :2439-2444

[8] COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer [J].

Forbes, Simon A. ;

Tang, Gurpreet ;

Bindal, Nidhi ;

Bamford, Sally ;

Dawson, Elisabeth ;

Cole, Charlotte ;

Kok, Chai Yin ;

Jia, Mingming ;

Ewing, Rebecca ;

Menzies, Andrew ;

Teague, Jon W. ;

Stratton, Michael R. ;

Futreal, P. Andrew .

NUCLEIC ACIDS RESEARCH, 2010, 38 :D652-D657

[9] Clinical and Molecular Determinants of Clonal Evolution in Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria [J].

Gurnari, Carmelo ;

Pagliuca, Simona ;

Prata, Pedro Henrique ;

Galimard, Jacques-Emmanuel ;

Catto, Luiz Fernando B. ;

Larcher, Lise ;

Sebert, Marie ;

Allain, Vincent ;

Patel, Bhumika J. ;

Durmaz, Arda ;

Pinto, Andre L. ;

Inacio, Mariana C. B. ;

Hernandez, Lucie ;

Dhedin, Nathalie ;

Caillat-Zucman, Sophie ;

Clappier, Emmanuelle ;

de Fontbrune, Flore Sicre ;

Voso, Maria Teresa ;

Visconte, Valeria ;

de Latour, Regis Peffault ;

Soulier, Jean ;

Calado, Rodrigo T. ;

Socie, Gerard ;

Maciejewski, Jaroslaw P. .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (01) :132-+

[10] A study of Telomerase Reverse Transcriptase rare variants in myeloid neoplasia [J].

Gurnari, Carmelo ;

Wahida, Adam ;

Pagliuca, Simona ;

Durmaz, Arda ;

Zawit, Misam ;

Haferlach, Torsten ;

Maciejewski, Jaroslaw P. ;

Visconte, Valeria .

HEMATOLOGICAL ONCOLOGY, 2022, 40 (04) :812-817

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