Browse > Article
http://dx.doi.org/10.14348/molcells.2019.0252

The Clinical, Molecular, and Mechanistic Basis of RUNX1 Mutations Identified in Hematological Malignancies  

Yokota, Asumi (Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center)
Huo, Li (Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center)
Lan, Fengli (Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center)
Wu, Jianqiang (Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center)
Huang, Gang (Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center)
Publication Information
Molecules and Cells / v.43, no.2, 2020 , pp. 145-152 More about this Journal
Abstract
RUNX1 plays an important role in the regulation of normal hematopoiesis. RUNX1 mutations are frequently found and have been intensively studied in hematological malignancies. Germline mutations in RUNX1 cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Somatic mutations of RUNX1 are observed in various types of hematological malignancies, such as AML, acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML), and congenital bone marrow failure (CBMF). Here, we systematically review the clinical and molecular characteristics of RUNX1 mutations, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies to target RUNX1-mutated cases of hematological malignancies.
Keywords
clinical incidence and prognosis; pathogenesis; RUNX1 mutations; targeted therapy;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Mendler, J.H., Maharry, K., Radmacher, M.D., Mrozek, K., Becker, H., Metzeler, K.H., Schwind, S., Whitman, S.P., Khalife, J., Kohlschmidt, J., et al. (2012). RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. J. Clin. Oncol. 30, 3109-3118.   DOI
2 Migas, A., Savva, N., Mishkova, O., and Aleinikova, O.V. (2011). AML1/RUNX1 gene point mutations in childhood myeloid malignancies. Pediatr. Blood Cancer 57, 583-587.   DOI
3 Motoda, L., Osato, M., Yamashita, N., Jacob, B., Chen, L.Q., Yanagida, M., Ida, H., Wee, H.J., Sun, A.X., Taniuchi, I., et al. (2007). Runx1 protects hematopoietic stem/progenitor cells from oncogenic insult. Stem Cells (Dayton, Ohio) 25, 2976-2986.   DOI
4 Niimi, H., Harada, H., Harada, Y., Ding, Y., Imagawa, J., Inaba, T., Kyo, T., and Kimura, A. (2006). Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia 20, 635-644.   DOI
5 Nishimoto, N., Imai, Y., Ueda, K., Nakagawa, M., Shinohara, A., Ichikawa, M., Nannya, Y., and Kurokawa, M. (2010). T cell acute lymphoblastic leukemia arising from familial platelet disorder. Int. J. Hematol. 92, 194-197.   DOI
6 Osato, M. (2004). Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia. Oncogene 23, 4284-4296.   DOI
7 Hong, D., Messier, T.L., Tye, C.E., Dobson, J.R., Fritz, A.J., Sikora, K.R., Browne, G., Stein, J.L., Lian, J.B., and Stein, G.S. (2017). Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition. Oncotarget 8, 17610-17627.   DOI
8 Harada, H., Harada, Y., Niimi, H., Kyo, T., Kimura, A., and Inaba, T. (2004). High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood 103, 2316-2324.   DOI
9 Harada, H., Harada, Y., Tanaka, H., Kimura, A., and Inaba, T. (2003). Implications of somatic mutations in the AML1 gene in radiationassociated and therapy-related myelodysplastic syndrome/acute myeloid leukemia. Blood 101, 673-680.   DOI
10 Hayashi, Y., Harada, Y., Huang, G., and Harada, H. (2017). Myeloid neoplasms with germ line RUNX1 mutation. Int. J. Hematol. 106, 183-188.   DOI
11 Hou, H.A., Kuo, Y.Y., Liu, C.Y., Lee, M.C., Tang, J.L., Chen, C.Y., Chou, W.C., Huang, C.F., Lee, F.Y., Liu, M.C., et al. (2011). Distinct association between aberrant methylation of Wnt inhibitors and genetic alterations in acute myeloid leukaemia. Br. J. Cancer 105, 1927-1933.   DOI
12 Ichikawa, M., Asai, T., Saito, T., Seo, S., Yamazaki, I., Yamagata, T., Mitani, K., Chiba, S., Ogawa, S., Kurokawa, M., et al. (2004). AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat. Med. 10, 299-304.   DOI
13 Ito, Y., Bae, S.C., and Chuang, L.S. (2015). The RUNX family: developmental regulators in cancer. Nat. Rev. Cancer 15, 81-95.   DOI
14 Mangan, J.K. and Speck, N.A. (2011). RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making. Crit. Rev. Oncog. 16, 77-91.   DOI
15 Harada, H. and Harada, Y. (2015). Recent advances in myelodysplastic syndromes: molecular pathogenesis and its implications for targeted therapies. Cancer Sci. 106, 329-336.   DOI
16 Klampfl, T., Harutyunyan, A., Berg, T., Gisslinger, B., Schalling, M., Bagienski, K., Olcaydu, D., Passamonti, F., Rumi, E., Pietra, D., et al. (2011). Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 118, 167-176.
17 Kuo, M.C., Liang, D.C., Huang, C.F., Shih, Y.S., Wu, J.H., Lin, T.L., and Shih, L.Y. (2009). RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia 23, 1426-1431.   DOI
18 Kutler, D.I., Singh, B., Satagopan, J., Batish, S.D., Berwick, M., Giampietro, P.F., Hanenberg, H., and Auerbach, A.D. (2003). A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood 101, 1249-1256.   DOI
19 Latger-Cannard, V., Philippe, C., Bouquet, A., Baccini, V., Alessi, M.C., Ankri, A., Bauters, A., Bayart, S., Cornillet-Lefebvre, P., Daliphard, S., et al. (2016). Haematological spectrum and genotype-phenotype correlations in nine unrelated families with RUNX1 mutations from the French network on inherited platelet disorders. Orphanet J. Rare Dis. 11, 49.   DOI
20 Osato, M., Asou, N., Abdalla, E., Hoshino, K., Yamasaki, H., Okubo, T., Suzushima, H., Takatsuki, K., Kanno, T., Shigesada, K., et al. (1999). Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. Blood 93, 1817-1824.   DOI
21 Owen, C., Barnett, M., and Fitzgibbon, J. (2008a). Familial myelodysplasia and acute myeloid leukaemia--a review. Br. J. Haematol. 140, 123-132.   DOI
22 Owen, C.J., Toze, C.L., Koochin, A., Forrest, D.L., Smith, C.A., Stevens, J.M., Jackson, S.C., Poon, M.C., Sinclair, G.D., Leber, B., et al. (2008b). Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood 112, 4639-4645.   DOI
23 Pedersen-Bjergaard, J., Andersen, M.K., Andersen, M.T., and Christiansen, D.H. (2008). Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 22, 240-248.   DOI
24 Ding, Y., Harada, Y., Imagawa, J., Kimura, A., and Harada, H. (2009). AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 114, 5201-5205.   DOI
25 Corm, S., Biggio, V., Roche-Lestienne, C., Lai, J.L., Yakoub-Agha, I., Philippe, N., Nicolini, F.E., Facon, T., and Preudhomme, C. (2005). Coexistence of AML1/RUNX1 and BCR-ABL point mutations in an imatinib-resistant form of CML. Leukemia 19, 1991-1992.   DOI
26 Deltcheva, E. and Nimmo, R. (2017). RUNX transcription factors at the interface of stem cells and cancer. Biochem. J. 474, 1755-1768.   DOI
27 Dicker, F., Haferlach, C., Sundermann, J., Wendland, N., Weiss, T., Kern, W., Haferlach, T., and Schnittger, S. (2010). Mutation analysis for RUNX1, MLLPTD, FLT3-ITD, NPM1 and NRAS in 269 patients with MDS or secondary AML. Leukemia 24, 1528-1532.   DOI
28 Godley, L.A. (2014). Inherited predisposition to acute myeloid leukemia. Semin. Hematol. 51, 306-321.   DOI
29 Gaidzik, V.I., Bullinger, L., Schlenk, R.F., Zimmermann, A.S., Rock, J., Paschka, P., Corbacioglu, A., Krauter, J., Schlegelberger, B., Ganser, A., et al. (2011). RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J. Clin. Oncol. 29, 1364-1372.   DOI
30 Gaidzik, V.I., Teleanu, V., Papaemmanuil, E., Weber, D., Paschka, P., Hahn, J., Wallrabenstein, T., Kolbinger, B., Kohne, C.H., Horst, H.A., et al. (2016). RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia 30, 2282.   DOI
31 Gohring, G., Karow, A., Steinemann, D., Wilkens, L., Lichter, P., Zeidler, C., Niemeyer, C., Welte, K., and Schlegelberger, B. (2007). Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis? Ann. Hematol. 86, 733-739.   DOI
32 Xu, F., Wu, L.Y., He, Q., Wu, D., Zhang, Z., Song, L.X., Zhao, Y.S., Su, J.Y., Zhou, L.Y., Guo, J., et al. (2017). Exploration of the role of gene mutations in myelodysplastic syndromes through a sequencing design involving a small number of target genes. Sci. Rep. 7, 43113.   DOI
33 Taniuchi, I., Osato, M., Egawa, T., Sunshine, M.J., Bae, S.C., Komori, T., Ito, Y., and Littman, D.R. (2002). Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111, 621-633.   DOI
34 Thoennissen, N.H., Krug, U.O., Lee, D.H., Kawamata, N., Iwanski, G.B., Lasho, T., Weiss, T., Nowak, D., Koren-Michowitz, M., Kato, M., et al. (2010). Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood 115, 2882-2890.   DOI
35 Tsai, S.C., Shih, L.Y., Liang, S.T., Huang, Y.J., Kuo, M.C., Huang, C.F., Shih, Y.S., Lin, T.H., Chiu, M.C., and Liang, D.C. (2015). Biological activities of RUNX1 mutants predict secondary acute leukemia transformation from chronic myelomonocytic leukemia and myelodysplastic syndromes. Clin. Cancer Res. 21, 3541-3551.   DOI
36 Vormittag-Nocito, E., Ni, H., Schmidt, M.L., and Lindgren, V. (2019). Thrombocytopenia and predisposition to acute myeloid leukemia due to mosaic ring 21 with loss of RUNX1: cytogenetic and molecular characterization. Mol. Syndromol. 9, 306-311.   DOI
37 Wu, D., Ozaki, T., Yoshihara, Y., Kubo, N., and Nakagawara, A. (2013). Runtrelated transcription factor 1 (RUNX1) stimulates tumor suppressor p53 protein in response to DNA damage through complex formation and acetylation. J. Biol. Chem. 288, 1353-1364.   DOI
38 Yoshimi, A., Toya, T., Kawazu, M., Ueno, T., Tsukamoto, A., Iizuka, H., Nakagawa, M., Nannya, Y., Arai, S., Harada, H., et al. (2014). Recurrent CDC25C mutations drive malignant transformation in FPD/AML. Nat. Commun. 5, 4770.   DOI
39 Grossmann, V., Haferlach, C., Weissmann, S., Roller, A., Schindela, S., Poetzinger, F., Stadler, K., Bellos, F., Kern, W., Haferlach, T., et al. (2013). The molecular profile of adult T-cell acute lymphoblastic leukemia: mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL. Genes Chromosomes Cancer 52, 410-422.   DOI
40 Goyama, S., Huang, G., Kurokawa, M., and Mulloy, J.C. (2015). Posttranslational modifications of RUNX1 as potential anticancer targets. Oncogene 34, 3483-3492.   DOI
41 Grossmann, V., Kern, W., Harbich, S., Alpermann, T., Jeromin, S., Schnittger, S., Haferlach, C., Haferlach, T., and Kohlmann, A. (2011a). Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia. Haematologica 96, 1874-1877.   DOI
42 Haferlach, T., Stengel, A., Eckstein, S., Perglerova, K., Alpermann, T., Kern, W., Haferlach, C., and Meggendorfer, M. (2016). The new provisional WHO entity 'RUNX1 mutated AML' shows specific genetics but no prognostic influence of dysplasia. Leukemia 30, 2109-2112.   DOI
43 Grossmann, V., Kohlmann, A., Zenger, M., Schindela, S., Eder, C., Weissmann, S., Schnittger, S., Kern, W., Muller, M.C., Hochhaus, A., et al. (2011b). A deep-sequencing study of chronic myeloid leukemia patients in blast crisis (BC-CML) detects mutations in 76.9% of cases. Leukemia 25, 557-560.   DOI
44 Grossmann, V., Schnittger, S., Kohlmann, A., Eder, C., Roller, A., Dicker, F., Schmid, C., Wendtner, C.M., Staib, P., Serve, H., et al. (2012). A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 120, 2963-2972.
45 Haferlach, T., Nagata, Y., Grossmann, V., Okuno, Y., Bacher, U., Nagae, G., Schnittger, S., Sanada, M., Kon, A., Alpermann, T., et al. (2014). Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia 28, 241-247.   DOI
46 Quentin, S., Cuccuini, W., Ceccaldi, R., Nibourel, O., Pondarre, C., Pages, M.P., Vasquez, N., Dubois d'Enghien, C., Larghero, J., Peffault de Latour, R., et al. (2011). Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions. Blood 117, e161-e170.   DOI
47 Pedersen-Bjergaard, J., Christiansen, D.H., Desta, F., and Andersen, M.K. (2006). Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 20, 1943-1949.   DOI
48 Peng, Z.G., Zhou, M.Y., Huang, Y., Qiu, J.H., Wang, L.S., Liao, S.H., Dong, S., and Chen, G.Q. (2008). Physical and functional interaction of Runt-related protein 1 with hypoxia-inducible factor-1alpha. Oncogene 27, 839-847.   DOI
49 Preudhomme, C., Renneville, A., Bourdon, V., Philippe, N., Roche-Lestienne, C., Boissel, N., Dhedin, N., Andre, J.M., Cornillet-Lefebvre, P., Baruchel, A., et al. (2009). High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder. Blood 113, 5583-5587.   DOI
50 Preudhomme, C., Warot-Loze, D., Roumier, C., Grardel-Duflos, N., Garand, R., Lai, J.L., Dastugue, N., Macintyre, E., Denis, C., Bauters, F., et al. (2000). High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21. Blood 96, 2862-2869.   DOI
51 Roche-Lestienne, C., Deluche, L., Corm, S., Tigaud, I., Joha, S., Philippe, N., Geffroy, S., Lai, J.L., Nicolini, F.E., and Preudhomme, C. (2008). RUNX1 DNAbinding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Blood 111, 3735-3741.   DOI
52 Ruggero, D. and Shimamura, A. (2014). Marrow failure: a window into ribosome biology. Blood 124, 2784-2792.   DOI
53 Schnittger, S., Dicker, F., Kern, W., Wendland, N., Sundermann, J., Alpermann, T., Haferlach, C., and Haferlach, T. (2011). RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 117, 2348-2357.   DOI
54 Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S.L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., et al. (2012). The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481, 157-163.   DOI
55 Zhao, L.J., Wang, Y.Y., Li, G., Ma, L.Y., Xiong, S.M., Weng, X.Q., Zhang, W.N., Wu, B., Chen, Z., and Chen, S.J. (2012). Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood 119, 2873-2882.   DOI
56 Zharlyganova, D., Harada, H., Harada, Y., Shinkarev, S., Zhumadilov, Z., Zhunusova, A., Tchaizhunusova, N.J., Apsalikov, K.N., Kemaikin, V., Zhumadilov, K., et al. (2008). High frequency of AML1/RUNX1 point mutations in radiation-associated myelodysplastic syndrome around Semipalatinsk nuclear test site. J. Radiat. Res. 49, 549-555.   DOI
57 Hayashi, Y., Yokota, A., Harada, H., and Huang, G. (2019). Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1alpha in cancer. Cancer Sci. 110, 1510-1517.   DOI
58 Antony-Debre, I., Duployez, N., Bucci, M., Geffroy, S., Micol, J.B., Renneville, A., Boissel, N., Dhedin, N., Rea, D., Nelken, B., et al. (2016). Somatic mutations associated with leukemic progression of familial platelet disorder with predisposition to acute myeloid leukemia. Leukemia 30, 999-1002.   DOI
59 Schlegelberger, B. and Heller, P.G. (2017). RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM). Semin. Hematol. 54, 75-80.   DOI
60 Schmidt, M., Rinke, J., Schafer, V., Schnittger, S., Kohlmann, A., Obstfelder, E., Kunert, C., Ziermann, J., Winkelmann, N., Eigendorff, E., et al. (2014). Molecular-defined clonal evolution in patients with chronic myeloid leukemia independent of the BCR-ABL status. Leukemia 28, 2292-2299.   DOI
61 Shiba, N., Hasegawa, D., Park, M.J., Murata, C., Sato-Otsubo, A., Ogawa, C., Manabe, A., Arakawa, H., Ogawa, S., and Hayashi, Y. (2012). CBL mutation in chronic myelomonocytic leukemia secondary to familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML). Blood 119, 2612-2614.   DOI
62 Shih, A.H., Chung, S.S., Dolezal, E.K., Zhang, S.J., Abdel-Wahab, O.I., Park, C.Y., Nimer, S.D., Levine, R.L., and Klimek, V.M. (2013). Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Haematologica 98, 908-912.   DOI
63 Singhal, D., Wee, L.Y.A., Kutyna, M.M., Chhetri, R., Geoghegan, J., Schreiber, A.W., Feng, J., Wang, P.P., Babic, M., Parker, W.T., et al. (2019). The mutational burden of therapy-related myeloid neoplasms is similar to primary myelodysplastic syndrome but has a distinctive distribution. Leukemia 33, 2842-2853.   DOI
64 Branford, S., Wang, P., Yeung, D.T., Thomson, D., Purins, A., Wadham, C., Shahrin, N.H., Marum, J.E., Nataren, N., Parker, W.T., et al. (2018). Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease. Blood 132, 948-961.
65 Baer, C., Muehlbacher, V., Kern, W., Haferlach, C., and Haferlach, T. (2018). Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2. Haematologica 103, e348-e350.   DOI
66 Beer, P.A., Delhommeau, F., LeCouedic, J.P., Dawson, M.A., Chen, E., Bareford, D., Kusec, R., McMullin, M.F., Harrison, C.N., Vannucchi, A.M., et al. (2010). Two routes to leukemic transformation after a JAK2 mutationpositive myeloproliferative neoplasm. Blood 115, 2891-2900.   DOI
67 Bejar, R., Stevenson, K.E., Caughey, B.A., Abdel-Wahab, O., Steensma, D.P., Galili, N., Raza, A., Kantarjian, H., Levine, R.L., Neuberg, D., et al. (2012). Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J. Clin. Oncol. 30, 3376-3382.   DOI
68 Bullinger, L., Dohner, K., and Dohner, H. (2017). Genomics of acute myeloid leukemia diagnosis and pathways. J. Clin. Oncol. 35, 934-946.   DOI
69 Cai, X., Gao, L., Teng, L., Ge, J., Oo, Z.M., Kumar, A.R., Gilliland, D.G., Mason, P.J., Tan, K., and Speck, N.A. (2015). Runx1 deficiency decreases ribosome biogenesis and confers stress resistance to hematopoietic stem and progenitor cells. Cell Stem Cell 17, 165-177.   DOI
70 Skokowa, J., Steinemann, D., Katsman-Kuipers, J.E., Zeidler, C., Klimenkova, O., Klimiankou, M., Unalan, M., Kandabarau, S., Makaryan, V., Beekman, R., et al. (2014). Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. Blood 123, 2229-2237.   DOI
71 Cancer Genome Atlas Research Network, Ley, T.J., Miller, C., Ding, L., Raphael, B.J., Mungall, A.J., Robertson, A., Hoadley, K., Triche, T.J., Jr., Laird, P.W., et al. (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059-2074.   DOI
72 Chao, M.M., Thomay, K., Goehring, G., Wlodarski, M., Pastor, V., Schlegelberger, B., Schindler, D., Kratz, C.P., and Niemeyer, C. (2017). Mutational spectrum of Fanconi anemia associated myeloid neoplasms. Klin. Padiatr. 229, 329-334.   DOI
73 Cavalcante de Andrade Silva, M., Krepischi, A.C.V., Kulikowski, L.D., Zanardo, E.A., Nardinelli, L., Leal, A.M., Costa, S.S., Muto, N.H., Rocha, V., and Velloso, E. (2018). Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia. Cancer Genet. 222-223, 32-37.   DOI
74 Cazzola, M., Della Porta, M.G., and Malcovati, L. (2013). The genetic basis of myelodysplasia and its clinical relevance. Blood 122, 4021-4034.
75 Cerquozzi, S. and Tefferi, A. (2015). Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 5, e366.   DOI
76 Chen, C.Y., Lin, L.I., Tang, J.L., Ko, B.S., Tsay, W., Chou, W.C., Yao, M., Wu, S.J., Tseng, M.H., and Tien, H.F. (2007). 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. 139, 405-414.   DOI
77 Stengel, A., Kern, W., Meggendorfer, M., Haferlach, T., and Haferlach, C. (2019). RUNX1 mutations in MDS, s-AML, and de novo AML: differences in accompanying genetic alterations and outcome. Leuk. Lymphoma 60, 1334-1336.   DOI
78 Song, W.J., Sullivan, M.G., Legare, R.D., Hutchings, S., Tan, X., Kufrin, D., Ratajczak, J., Resende, I.C., Haworth, C., Hock, R., et al. (1999). Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat. Genet. 23, 166-175.   DOI
79 Sood, R., Kamikubo, Y., and Liu, P. (2017). Role of RUNX1 in hematological malignancies. Blood 129, 2070-2082.   DOI
80 Steensma, D.P., Gibbons, R.J., Mesa, R.A., Tefferi, A., and Higgs, D.R. (2005). Somatic point mutations in RUNX1/CBFA2/AML1 are common in highrisk myelodysplastic syndrome, but not in myelofibrosis with myeloid metaplasia. Eur. J. Haematol. 74, 47-53.   DOI
81 Stengel, A., Kern, W., Meggendorfer, M., Nadarajah, N., Perglerova, K., Haferlach, T., and Haferlach, C. (2018). Number of RUNX1 mutations, wildtype allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia 32, 295-302.   DOI
82 Tang, J.L., Hou, H.A., Chen, C.Y., Liu, C.Y., Chou, W.C., Tseng, M.H., Huang, C.F., Lee, F.Y., Liu, M.C., Yao, M., et al. (2009). AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 114, 5352-5361.   DOI
83 Christiansen, D.H., Andersen, M.K., and Pedersen-Bjergaard, J. (2004). Mutations of AML1 are common in therapy-related myelodysplasia following therapy with alkylating agents and are significantly associated with deletion or loss of chromosome arm 7q and with subsequent leukemic transformation. Blood 104, 1474-1481.
84 Churpek, J.E., Lorenz, R., Nedumgottil, S., Onel, K., Olopade, O.I., Sorrell, A., Owen, C.J., Bertuch, A.A., and Godley, L.A. (2013). Proposal for the clinical detection and management of patients and their family members with familial myelodysplastic syndrome/acute leukemia predisposition syndromes. Leuk. Lymphoma 54, 28-35.   DOI
85 Strati, P., Tang, G., Duose, D.Y., Mallampati, S., Luthra, R., Patel, K.P., Hussaini, M., Mirza, A.S., Komrokji, R.S., Oh, S., et al. (2018). Myeloid/lymphoid neoplasms with FGFR1 rearrangement. Leuk. Lymphoma 59, 1672-1676.   DOI