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Myelodysplastic syndrome

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

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Fig. 1: Clinical and mutational characteristics of patients with germline and somatic RUNX1 mutations.

References

  1. Imperato MR, Cauchy P, Obier N, Bonifer C. The RUNX1-PU.1 axis in the control of hematopoiesis. Int J Hematol. 2015;101:319–29.

  2. Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet. 1999;23:166–75.

    Article  CAS  Google Scholar 

  3. Owen C, Barnett M, Fitzgibbon J. Familial myelodysplasia and acute myeloid leukaemia—a review. Br J Haematol. 2008;140:123–32.

    Article  CAS  Google Scholar 

  4. Churpek JE, Pyrtel K, Kanchi KL, Shao J, Koboldt D, Miller CA, et al. Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood. 2015;126:2484–90.

    Article  CAS  Google Scholar 

  5. Gaidzik VI, Teleanu V, Papaemmanuil E, Weber D, Paschka P, Hahn J, et al. RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia. 2016;30:2282.

    Article  CAS  Google Scholar 

  6. Chen CY, Lin LI, Tang JL, Ko BS, Tsay W, Chou WC, et al. RUNX1 gene mutation in primary myelodysplastic syndrome—the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome. Br J Haematol. 2007;139:405–14.

    Article  CAS  Google Scholar 

  7. Patnaik MM, Tefferi A. Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia. Blood Cancer J. 2016;6:e393.

    Article  CAS  Google Scholar 

  8. Tefferi A, Lasho TL, Guglielmelli P, Finke CM, Rotunno G, Elala Y, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016;1:21–30.

    Article  CAS  Google Scholar 

  9. Elena C, Galli A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128:1408–17.

    Article  CAS  Google Scholar 

  10. Kwok B, Hall JM, Witte JS, Xu Y, Reddy P, Lin K, et al. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood. 2015;126:2355–61.

    Article  CAS  Google Scholar 

  11. Malcovati L, Galli A, Travaglino E, Ambaglio I, Rizzo E, Molteni E, et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood. 2017;129:3371–8.

    Article  CAS  Google Scholar 

  12. Patnaik MM, Lasho TL, Vijayvargiya P, Finke CM, Hanson CA, Ketterling RP, et al. Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia. Blood Cancer J. 2016;6:e385.

    Article  CAS  Google Scholar 

  13. Stengel A, Kern W, Meggendorfer M, Nadarajah N, Perglerova K, Haferlach T, et al. Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia. 2018;32:295–302.

    Article  CAS  Google Scholar 

  14. Stockley J, Morgan NV, Bem D, Lowe GC, Lordkipanidze M, Dawood B, et al. Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects. Blood. 2013;122:4090–3.

    Article  CAS  Google Scholar 

  15. Duployez N, Martin JE, Khalife-Hachem S, Benkhelil R, Saada V, Marzac C, et al. Germline RUNX1 intragenic deletion: implications for accurate diagnosis of FPD/AML. Hemasphere. 2019;3:e203.

    Article  Google Scholar 

  16. Jongmans MC, Kuiper RP, Carmichael CL, Wilkins EJ, Dors N, Carmagnac A, 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;24:242–6.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the “Henry J Predolin Foundation” for Leukemia research for helping fund this research. We would also like to acknowledge all participating patients and their family members who have consented for this study.

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Authors and Affiliations

  1. Mayo Clinic Alix School of Medicine, Rochester, MN, USA

    Emma C. DiFilippo

  2. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Giacomo Coltro, Ryan M. Carr, Abhishek A. Mangaonkar, Moritz Binder, Naseema Gangat, Alexandra Wolanskyj, Rajiv K. Pruthi, Terra Lasho, Christy Finke, Ayalew Tefferi & Animesh Pardanani

  3. Division of Pediatric Hematology, Mayo Clinic, Rochester, MN, USA

    Shakila P. Khan, Vilmarie Rodriguez & Mrinal M. Patnaik

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Dong Chen, Rong He & David S. Viswanatha

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  1. Emma C. DiFilippo
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  2. Giacomo Coltro
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Corresponding author

Correspondence to Mrinal M. Patnaik.

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DiFilippo, E.C., Coltro, G., Carr, R.M. 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 34, 2519–2524 (2020). https://doi.org/10.1038/s41375-020-0752-x

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