GATA2 Monoallelic Expression Underlies Reduced Penetrance in Inherited GATA2-mutated MDS/AML

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2018 May 12

PMID 29749400

Citations 41

Authors

Ahad F Al Seraihi

Ana Rio-Machin

Kiran Tawana

Csaba Bodor

Jun Wang

Ai Nagano

James A Heward

Sameena Iqbal

Steven Best

Nicholas Lea

Donal McLornan

Emilia J Kozyra

Marcin W Wlodarski

Charlotte M Niemeyer

Hamish Scott

Chris Hahn

Alicia Ellison

Hemanth Tummala

Shirleny Romualdo Cardoso

Tom Vulliamy

Inderjeet Dokal

Tom Butler

Matthew Smith

Jamie Cavenagh

Jude Fitzgibbon

Affiliations

Soon will be listed here.

Citing Articles

GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome.

Largeaud L, Fregona V, Jamrog L, Hamelle C, Dufrechou S, Prade N Blood Cancer J. 2025; 15(1):7.

PMID: 39885120 PMC: 11782539. DOI: 10.1038/s41408-025-01213-z.

PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.

Katerndahl C, Rogers O, Day R, Xu Z, Helton N, Ramakrishnan S Proc Natl Acad Sci U S A. 2024; 121(18):e2317690121.

PMID: 38648485 PMC: 11067031. DOI: 10.1073/pnas.2317690121.

Pathogenic GATA2 genetic variants utilize an obligate enhancer mechanism to distort a multilineage differentiation program.

Katsumura K, Liu P, Kim J, Mehta C, Bresnick E Proc Natl Acad Sci U S A. 2024; 121(10):e2317147121.

PMID: 38422019 PMC: 10927522. DOI: 10.1073/pnas.2317147121.

mutant variant allele frequency may reflect prognosis in Chinese adult patients with de novo cytogenetically normal acute myeloid leukemia.

Ren H, Hong M, Feng J, Hao Z, Chen X, Liang F Biomol Biomed. 2024; 24(4):982-989.

PMID: 38416121 PMC: 11293240. DOI: 10.17305/bb.2024.10244.

Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome.

Arai H, Matsui H, Chi S, Utsu Y, Masuda S, Aotsuka N Int J Mol Sci. 2024; 25(1).

PMID: 38203823 PMC: 10779750. DOI: 10.3390/ijms25010652.

References

Pastor V, Hirabayashi S, Karow A, Wehrle J, Kozyra E, Nienhold R . Mutational landscape in children with myelodysplastic syndromes is distinct from adults: specific somatic drivers and novel germline variants. Leukemia. 2016; 31(3):759-762. DOI: 10.1038/leu.2016.342. View

Hsu A, Johnson K, Falcone E, Sanalkumar R, Sanchez L, Hickstein D . GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome. Blood. 2013; 121(19):3830-7, S1-7. PMC: 3650705. DOI: 10.1182/blood-2012-08-452763. View

Chong C, Venugopal P, Stokes P, Lee Y, Brautigan P, Yeung D . Differential effects on gene transcription and hematopoietic differentiation correlate with GATA2 mutant disease phenotypes. Leukemia. 2017; 32(1):194-202. PMC: 5770593. DOI: 10.1038/leu.2017.196. View

Nickels E, Soodalter J, Churpek J, Godley L . Recognizing familial myeloid leukemia in adults. Ther Adv Hematol. 2013; 4(4):254-69. PMC: 3734901. DOI: 10.1177/2040620713487399. View

Hahn C, Chong C, Carmichael C, Wilkins E, Brautigan P, Li X . Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet. 2011; 43(10):1012-7. PMC: 3184204. DOI: 10.1038/ng.913. View

Celton M, Forest A, Gosse G, Lemieux S, Hebert J, Sauvageau G . Epigenetic regulation of GATA2 and its impact on normal karyotype acute myeloid leukemia. Leukemia. 2014; 28(8):1617-26. DOI: 10.1038/leu.2014.67. View

Bodor C, Renneville A, Smith M, Charazac A, Iqbal S, Etancelin P . Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival. Haematologica. 2012; 97(6):890-4. PMC: 3366655. DOI: 10.3324/haematol.2011.054361. View

Arber D, Orazi A, Hasserjian R, Thiele J, Borowitz M, Le Beau M . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20):2391-405. DOI: 10.1182/blood-2016-03-643544. View

. How I diagnose and manage individuals at risk for inherited myeloid malignancies. Blood. 2016; 128(14):1800-1813. PMC: 5813725. DOI: 10.1182/blood-2016-05-670240. View

10.

Wang X, Muramatsu H, Okuno Y, Sakaguchi H, Yoshida K, Kawashima N . GATA2 and secondary mutations in familial myelodysplastic syndromes and pediatric myeloid malignancies. Haematologica. 2015; 100(10):e398-401. PMC: 4591774. DOI: 10.3324/haematol.2015.127092. View

11.

Rose N, Klose R . Understanding the relationship between DNA methylation and histone lysine methylation. Biochim Biophys Acta. 2014; 1839(12):1362-72. PMC: 4316174. DOI: 10.1016/j.bbagrm.2014.02.007. View

12.

Boultwood J, Perry J, Pellagatti A, Fernandez-Mercado M, Fernandez-Santamaria C, Calasanz M . Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia. 2010; 24(5):1062-5. DOI: 10.1038/leu.2010.20. View

13.

Cooper D, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H . Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum Genet. 2013; 132(10):1077-130. PMC: 3778950. DOI: 10.1007/s00439-013-1331-2. View

14.

West R, Hsu A, Holland S, Cuellar-Rodriguez J, Hickstein D . Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. Haematologica. 2013; 99(2):276-81. PMC: 3912957. DOI: 10.3324/haematol.2013.090217. View

15.

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View

16.

Cortes-Lavaud X, Landecho M, Maicas M, Urquiza L, Merino J, Moreno-Miralles I . GATA2 germline mutations impair GATA2 transcription, causing haploinsufficiency: functional analysis of the p.Arg396Gln mutation. J Immunol. 2015; 194(5):2190-8. DOI: 10.4049/jimmunol.1401868. View