Familial platelet disorder due to germline exonic deletions in RUNX1: a diagnostic challenge with distinct alterations of the transcript isoform equilibrium

References

• Beri-Dexheimer M, Latger-Cannard V, Philippe C, et al. Clinical phenotype of germline RUNX1 haploinsufficiency: from point mutations to large genomic deletions. Eur J Hum Genet. 2008;16(8):1014–1018.
   PubMed Web of Science ®Google Scholar
• Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.
   PubMed Web of Science ®Google Scholar
• Wu D, Luo X, Feurstein S, et al. How I curate: applying American Society of Hematology-Clinical genome resource myeloid malignancy variant curation expert panel rules for RUNX1 variant curation for germline predisposition to myeloid malignancies. Haematologica. 2020;105(4):870–887.
   PubMed Web of Science ®Google Scholar
• Klco JM, Mullighan CG. Advances in germline predisposition to acute leukaemias and myeloid neoplasms. Nat Rev Cancer. 2021;21(2):122–137.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–3627.
   PubMed Web of Science ®Google Scholar
• Gaidzik VI, Teleanu V, Papaemmanuil E, et al. RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia. 2016;30(11):2160–2168.
   PubMed Web of Science ®Google Scholar
• Lam K, Zhang DE. RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Front Biosci (Landmark Ed). 2012;17(3):1120–1139.
   PubMedGoogle Scholar
• Nottingham WT, Jarratt A, Burgess M, et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer. Blood. 2007;110(13):4188–4197.
   PubMed Web of Science ®Google Scholar
• Bee T, Ashley ELK, Bickley SRB, et al. The mouse Runx1 + 23 hematopoietic stem cell enhancer confers hematopoietic specificity to both Runx1 promoters. Blood. 2009;113(21):5121–5124.
   PubMed Web of Science ®Google Scholar
• Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23(2):166–175.
   PubMed Web of Science ®Google Scholar
• Human Gene Mutation Database (HGMD); 2022. Available from: http://www.hgmd.cf.ac.uk/ac/index.php
   Google Scholar
• Duployez N, Martin J, Khalife-Hachem S, et al. Germline RUNX1 intragenic deletion implications for accurate diagnosis of FPD/AML. Hemasphere. 2019;3(3):e203.
   PubMed Web of Science ®Google Scholar
• Rio-Machin A, Vulliamy T, Hug N, et al. The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants. Nat Commun. 2020;11(1):1044.
   PubMed Web of Science ®Google Scholar
• Sakurai M, Kasahara H, Yoshida K, et al. Genetic basis of myeloid transformation in familial platelet disorder/acute myeloid leukemia patients with haploinsufficient RUNX1 allele. Blood Cancer J. 2016;6(2):e392.
   PubMedGoogle Scholar
• Cavalcante de Andrade Silva M, Krepischi ACV, Kulikowski LD, et al. Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia. Cancer Genet. 2018;222–223:32–37.
   PubMed Web of Science ®Google Scholar
• Kanagal-Shamanna R, Loghavi S, DiNardo CD, et al. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation. Haematologica. 2017;102(10):1661–1670.
   PubMed Web of Science ®Google Scholar
• Homan CC, King-Smith SL, Lawrence DM, et al. The RUNX1 database (RUNX1db): establishment of an expert curated RUNX1 registry and genomics database as a public resource for familial platelet disorder with myeloid malignancy. Haematologica. 2021;106(11):3004–3007.
   PubMed Web of Science ®Google Scholar
• Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45.
   PubMed Web of Science ®Google Scholar
• Godley LA, Shimamura A. Genetic predisposition to hematologic malignancies: management and surveillance. Blood. 2017;130(4):424–432.
   PubMed Web of Science ®Google Scholar
• Baliakas P, Tesi B, Wartiovaara-Kautto U, et al. Nordic guidelines for germline predisposition to myeloid neoplasms in adults: recommendations for genetic diagnosis, clinical management and follow-up. Hemasphere. 2019;3(6):e321.
   PubMed Web of Science ®Google Scholar
• Furutani E, Shimamura A. Germline genetic predisposition to hematologic malignancy. J Clin Oncol. 2017;35(9):1018–1028.
   PubMed Web of Science ®Google Scholar
• Brown AL, Arts P, Carmichael CL, et al. RUNX1-mutated families show phenotype heterogeneity and a somatic mutation profile unique to germline predisposed AML. Blood Adv. 2020;4(6):1131–1144.
   PubMed Web of Science ®Google Scholar
• Guidugli L, Johnson AK, Alkorta-Aranburu G, et al. Clinical utility of gene panel-based testing for hereditary myelodysplastic syndrome/acute leukemia predisposition syndromes. Leukemia. 2017;31(5):1226–1229.
   PubMed Web of Science ®Google Scholar
• DiFilippo EC, Coltro G, Carr RM, et al. Spectrum of abnormalities and clonal transformation in germline RUNX1 familial platelet disorder and a genomic comparative analysis with somatic RUNX1 mutations in MDS/MPN overlap neoplasms. Leukemia. 2020;34(9):2519–2524.
   PubMed Web of Science ®Google Scholar
• Jongmans MC, Kuiper RP, Carmichael CL, et al. Novel RUNX1 mutations in familial platelet disorder with enhanced risk for acute myeloid leukemia: clues for improved identification of the FPD/AML syndrome. Leukemia. 2010;24(1):242–246.
   PubMed Web of Science ®Google Scholar
• Rampersaud E, Ziegler DS, Iacobucci I, et al. Germline deletion of ETV6 in familial acute lymphoblastic leukemia. Blood Adv. 2019;3(7):1039–1046.
   PubMed Web of Science ®Google Scholar
• Wlodarski MW, Collin M, Horwitz MS. GATA2 deficiency and related myeloid neoplasms. Semin Hematol. 2017;54(2):81–86.
   PubMed Web of Science ®Google Scholar
• Thiel A, Beier M, Ingenhag D, et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia. 2011;25(3):387–399.
   PubMed Web of Science ®Google Scholar
• Liu X, Zhang Q, Zhang DE, et al. Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis. Leukemia. 2009;23(4):739–745.
   PubMed Web of Science ®Google Scholar
• Sakurai H, Harada Y, Ogata Y, et al. Overexpression of RUNX1 short isoform has an important role in the development of myelodysplastic/myeloproliferative neoplasms. Blood Adv. 2017;1(18):1382–1386.
   PubMed Web of Science ®Google Scholar
• Tsuzuki S, Seto M. Expansion of functionally defined mouse hematopoietic stem and progenitor cells by a short isoform of RUNX1/AML1. Blood. 2012;119(3):727–735.
   PubMed Web of Science ®Google Scholar
• Tanaka T, Tanaka K, Ogawa S, et al. An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms. EMBO J. 1995;14(2):341–350.
   PubMed Web of Science ®Google Scholar
• Michaud JL, Wu F, Osato M, et al. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood. 2002;99(4):1364–1372.
   PubMed Web of Science ®Google Scholar
• Matheny CJ, Speck ME, Cushing PR, et al. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J. 2007;26(4):1163–1175.
   PubMed Web of Science ®Google Scholar
• Dowdy CR, Xie R, Frederick D, et al. Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation. Hum Mol Genet. 2010;19(6):1048–1057.
   PubMed Web of Science ®Google Scholar
• Draper JE, Sroczynska P, Leong HS, et al. Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival of megakaryocyte progenitors. Blood. 2017;130(3):271–284.
   PubMed Web of Science ®Google Scholar