{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:46:37Z","timestamp":1776185197023,"version":"3.50.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 103-2321-B-182-015, MOST 104-2321-B-182-005"],"award-info":[{"award-number":["MOST 103-2321-B-182-015, MOST 104-2321-B-182-005"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-EX103-10003NI"],"award-info":[{"award-number":["NHRI-EX103-10003NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["MOHW103-TD-B-111-09"],"award-info":[{"award-number":["MOHW103-TD-B-111-09"]}],"id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["OMRPG380031, OMRPG3C0021, and 101-1409B"],"award-info":[{"award-number":["OMRPG380031, OMRPG3C0021, and 101-1409B"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematol Oncol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Additional sex combs-like 1 (<jats:italic>ASXL1<\/jats:italic>) mutations have been described in all forms of myeloid neoplasms including chronic myelomonocytic leukemia (CMML) and associated with inferior outcomes, yet the molecular pathogenesis of <jats:italic>ASXL1<\/jats:italic> mutations (<jats:italic>ASXL1<\/jats:italic>-MT) remains poorly understood. Transformation of CMML to secondary AML (sAML) is one of the leading causes of death in CMML patients. Previously, we observed that transcription factor <jats:italic>RUNX1<\/jats:italic> mutations (<jats:italic>RUNX1<\/jats:italic>-MT) coexisted with <jats:italic>ASXL1<\/jats:italic>-MT in CMML and at myeloid blast phase of chronic myeloid leukemia. The contribution of <jats:italic>RUNX1<\/jats:italic> mutations in the pathogenesis of myeloid transformation in <jats:italic>ASXL1<\/jats:italic>-mutated leukemia, however, remains unclear.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To evaluate the leukemogenic role of RUNX1-MT in <jats:italic>ASXL1<\/jats:italic>-mutated cells, we co-expressed <jats:italic>RUNX1<\/jats:italic>-MT (R135T) and <jats:italic>ASXL1<\/jats:italic>-MT (R693X) in different cell lines and performed immunoblot, co-immunoprecipitation, gene expression microarray, quantitative RT-PCR, cell proliferation, differentiation, and clonogenic assays for in vitro functional analyses. The in vivo effect was investigated using the C57BL\/6 mouse bone marrow transplantation (BMT) model.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of <jats:italic>RUNX1<\/jats:italic> and <jats:italic>ASXL1<\/jats:italic> mutations played a critical role in leukemia transformation. The expression of <jats:italic>RUNX1<\/jats:italic> mutant in <jats:italic>ASXL1<\/jats:italic>-mutated myeloid cells augmented proliferation, blocked differentiation, and increased self-renewal activity. At 9\u2009months post-BMT, mice harboring combined <jats:italic>RUNX1<\/jats:italic> and <jats:italic>ASXL1<\/jats:italic> mutations developed disease characterized by marked splenomegaly, hepatomegaly, and leukocytosis with a shorter latency. Mice transduced with both <jats:italic>ASXL1<\/jats:italic> and <jats:italic>RUNX1<\/jats:italic> mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. Bone marrow samples from CMML showed that <jats:italic>ID1<\/jats:italic> overexpressed in coexisted mutations of <jats:italic>RUNX1<\/jats:italic> and <jats:italic>ASXL1<\/jats:italic> compared to normal control and either <jats:italic>RUNX1<\/jats:italic>-MT or <jats:italic>ASXL1<\/jats:italic>-MT samples. Moreover, the RUNX1 mutant protein was more stable than WT and increased HIF1-\u03b1 and its target <jats:italic>ID1<\/jats:italic> gene expression in <jats:italic>ASXL1<\/jats:italic> mutant cells.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The present study demonstrated the biological and functional evidence for the critical role of <jats:italic>RUNX1<\/jats:italic>-MT in <jats:italic>ASXL1<\/jats:italic>-mutated leukemia in the pathogenesis of myeloid malignancies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13045-019-0789-3","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T04:28:23Z","timestamp":1571804903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia"],"prefix":"10.1186","volume":"12","author":[{"given":"Rabindranath","family":"Bera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Chun","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Jung","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung-Huei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Chung","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-7922","authenticated-orcid":false,"given":"Lee-Yung","family":"Shih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"789_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1756-8722-5-12","volume":"5","author":"V Gelsi-Boyer","year":"2012","unstructured":"Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci MJ, Birnbaum D. Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol. 2012;5:12.","journal-title":"J Hematol Oncol"},{"key":"789_CR2","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ccr.2012.06.032","volume":"22","author":"O Abdel-Wahab","year":"2012","unstructured":"Abdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH, Pandey S, Patel JP, Chung YR, Koche R, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012;22:180\u201393.","journal-title":"Cancer Cell"},{"key":"789_CR3","first-page":"1398","volume":"96","author":"AM Vannucchi","year":"2011","unstructured":"Vannucchi AM, Biamonte F. Epigenetics and mutations in chronic myeloproliferative neoplasms. Haematologica. 2011;96:1398\u201302.","journal-title":"Haematologica"},{"key":"789_CR4","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/j.1365-2141.2010.08381.x","volume":"151","author":"V Gelsi-Boyer","year":"2010","unstructured":"Gelsi-Boyer V, Trouplin V, Roquain J, Ad\u00e9la\u00efde J, Carbuccia N, Esterni B, Finetti P, Murati A, Arnoulet C, Zerazhi H, et al. ASXL1 mutations is associated with poor prognosis and acute transformation in chronic myelomonocytic leukemia. Br J Haematol. 2010;151:365\u201375.","journal-title":"Br J Haematol"},{"key":"789_CR5","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/leu.2010.65","volume":"24","author":"J Boultwood","year":"2010","unstructured":"Boultwood J, Perry J, Zaman R, Fernandez-Santamaria C, Littlewood T, Kusec R, Pellagatti A, Wang L, Clark RE, Wainscoat JS. High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia. 2010;24:1139\u201345.","journal-title":"Leukemia"},{"key":"789_CR6","doi-asserted-by":"publisher","first-page":"3932","DOI":"10.1182\/blood-2010-10-311019","volume":"118","author":"AM Jankowska","year":"2011","unstructured":"Jankowska AM, Makishima H, Tiu RV, Szpurka H, Huang Y, Traina F, Visconte V, Sugimoto Y, Prince C, O'Keefe C, et al. Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood. 2011;118:3932\u201341.","journal-title":"Blood"},{"key":"789_CR7","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","volume":"127","author":"DA Arber","year":"2016","unstructured":"Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391\u201305.","journal-title":"Blood"},{"key":"789_CR8","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/ajh.23962","volume":"90","author":"MM Patnaik","year":"2015","unstructured":"Patnaik MM, Wassie EA, Lasho TL, Hanson CA, Ketterling R, Tefferi A. Blast transformation in chronic myelomonocytic leukemia: risk factors, genetic features, survival, and treatment outcome. Am J Hematol. 2015;90:411\u20136.","journal-title":"Am J Hematol"},{"key":"789_CR9","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/ajh.23846","volume":"89","author":"EA Wassie","year":"2014","unstructured":"Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, Ketterling RP, Solary E, Tefferi A, Patnaik MM. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol. 2014;89:1111\u20135.","journal-title":"Am J Hematol"},{"key":"789_CR10","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3324\/haematol.2011.051532","volume":"97","author":"M Pratcorona","year":"2012","unstructured":"Pratcorona M, Abbas S, Sanders MA, Koenders JE, Kavelaars FG, Erpelinck-Verschueren CA, Zeilemakers A, Lowenberg B, Valk PJ. Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. Haematologica. 2012;97:388\u201392.","journal-title":"Haematologica"},{"key":"789_CR11","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1182\/blood-2014-11-610543","volume":"125","author":"RC Lindsley","year":"2015","unstructured":"Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125:1367\u201376.","journal-title":"Blood"},{"key":"789_CR12","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1038\/s41467-018-05085-9","volume":"9","author":"S Asada","year":"2018","unstructured":"Asada S, Goyama S, Inoue D, Shikata S, Takeda R, Fukushima T, Yonezawa T, Fujino T, Hayashi Y, Kawabata KC, et al. Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nat Commun. 2018;9:2733.","journal-title":"Nat Commun"},{"key":"789_CR13","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s41375-018-0198-6","volume":"33","author":"M Uni","year":"2018","unstructured":"Uni M, Masamoto Y, Sato T, Kamikubo Y, Arai S, Hara E, Kurokawa M. Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification. Leukemia. 2018;33:191\u2013204.","journal-title":"Leukemia"},{"key":"789_CR14","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/leu.2014.301","volume":"29","author":"D Inoue","year":"2015","unstructured":"Inoue D, Kitaura J, Matsui H, Hou HA, Chou WC, Nagamachi A, Kawabata KC, Togami K, Nagase R, Horikawa S, et al. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS. Leukemia. 2015;29:847\u201357.","journal-title":"Leukemia"},{"key":"789_CR15","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1182\/blood-2017-06-789669","volume":"131","author":"H Yang","year":"2018","unstructured":"Yang H, Kurtenbach S, Guo Y, Lohse I, Durante MA, Li J, Li Z, Al-Ali H, Li L, Chen Z, et al. Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies. Blood. 2018;131:328\u201341.","journal-title":"Blood"},{"key":"789_CR16","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1038\/leu.2009.48","volume":"23","author":"MC Kuo","year":"2009","unstructured":"Kuo MC, Liang DC, Huang CF, Shih YS, Wu JH, Lin TL, Shih LY. RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia. 2009;23:1426\u201331.","journal-title":"Leukemia"},{"issue":"Suppl 1","key":"789_CR17","first-page":"477","volume":"100","author":"MC Kuo","year":"2015","unstructured":"Kuo MC, Shih LY, Tsai SC, Liang ST, Huang YJ, Shih YS, Lin TH, Lai CY, Liang DC. RUNX1 mutation and low RUNX1 transactivating activity predict higher risk of AML transformation and inferior leukemia-free survival in chronic myelomonocytic leukemia. Haematologica. 2015;100(Suppl 1):477.","journal-title":"Haematologica"},{"issue":"Suppl 1","key":"789_CR18","first-page":"448","volume":"101","author":"HW Kao","year":"2016","unstructured":"Kao HW, Kuo MC, Wang PN, Dunn P, Wu JH, Lai CL, Lin TH, Shih LY. Evolution of RUNX1 and ASXL1 mutations during progression of chronic myeloid leukemia to myeloid blast phase: an analysis of 52 matched paired samples at both. Haematologica. 2016;101(Suppl 1):448.","journal-title":"Haematologica"},{"key":"789_CR19","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1158\/1078-0432.CCR-14-2203","volume":"21","author":"SC Tsai","year":"2015","unstructured":"Tsai SC, Shih LY, Liang ST, Huang YJ, Kuo MC, Huang CF, Shih YS, Lin TH, Chiu MC, Liang DC. Biological activities of RUNX1 mutants predict secondary acute leukemia transformation from chronic myelomonocytic leukemia and myelodysplastic syndromes. Clin Cancer Res. 2015;21:3541\u201351.","journal-title":"Clin Cancer Res"},{"key":"789_CR20","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1182\/blood-2011-08-370981","volume":"119","author":"LJ Zhao","year":"2012","unstructured":"Zhao LJ, Wang YY, Li G, Ma LY, Xiong SM, Weng XQ, Zhang WN, Wu B, Chen Z, Chen SJ. Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood. 2012;119:2873\u201382.","journal-title":"Blood"},{"key":"789_CR21","doi-asserted-by":"publisher","first-page":"2988","DOI":"10.1182\/blood-2012-06-436782","volume":"121","author":"DC Liang","year":"2013","unstructured":"Liang DC, Liu HC, Yang CP, Jaing TH, Hung IJ, Yeh TC, Chen SH, Hou JY, Huang YJ, Shih YS, et al. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A. Blood. 2013;121:2988\u201395.","journal-title":"Blood"},{"key":"789_CR22","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.neo.2018.08.013","volume":"20","author":"R Bera","year":"2018","unstructured":"Bera R, Chiu MC, Huang YJ, Liang DC, Lee YS, Shih LY. Genetic and epigenetic perturbations by DNMT3A-R882 mutants impaired apoptosis through augmentation of PRDX2 in myeloid leukemia cells. Neoplasia. 2018;20:1106\u201320.","journal-title":"Neoplasia"},{"key":"789_CR23","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1172\/JCI42032","volume":"120","author":"A Bersenev","year":"2010","unstructured":"Bersenev A, Wu C, Balcerek J, Jing J, Kundu M, Blobel GA, Chikwava KR, Tong W. Lnk constrains myeloproliferative diseases in mice. J Clin Invest. 2010;120:2058\u201369.","journal-title":"J Clin Invest"},{"key":"789_CR24","first-page":"1384","volume":"91","author":"E Robert-Richard","year":"2006","unstructured":"Robert-Richard E, Ged C, Ortet J, Santarelli X, Lamrissi-Garcia I, de Verneuil H, Mazurier F. Human cell engraftment after busulfan or irradiation conditioning of NOD\/SCID mice. Haematologica. 2006;91:1384.","journal-title":"Haematologica"},{"key":"789_CR25","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/mt.2013.29","volume":"21","author":"FL Wilkinson","year":"2013","unstructured":"Wilkinson FL, Sergijenko A, Langford-Smith KJ, Malinowska M, Wynn RF, Bigger BW. Busulfan conditioning enhances engraftment of hematopoietic donor-derived cells in the brain compared with irradiation. Mol Ther. 2013;21:868\u201376.","journal-title":"Mol Ther"},{"key":"789_CR26","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1182\/blood-2009-02-205062","volume":"114","author":"F Navarro","year":"2009","unstructured":"Navarro F, Gutman D, Meire E, Caceres M, Rigoutsos I, Bentwich Z, Lieberman J. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood. 2009;114:2181\u201392.","journal-title":"Blood"},{"key":"789_CR27","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/sj.onc.1209119","volume":"25","author":"A Jacquel","year":"2006","unstructured":"Jacquel A, Herrant M, Defamie V, Belhacene N, Colosetti P, Marchetti S, Legros L, Deckert M, Mari B, Cassuto JP, et al. A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis. Oncogene. 2006;25:781\u201394.","journal-title":"Oncogene"},{"key":"789_CR28","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1182\/blood.V120.21.2393.2393","volume":"120","author":"R Bera","year":"2012","unstructured":"Bera R, Liang DC, Chiu MC, Huang YJ, Liang ST, Shih LY. PHD domain deletion mutations of ASXL1 promote myeloid leukemia transformation through epigenetic dysregulation and inhibit megakaryocytic differentiation through the inactivation of FOSB in K562 cells. Blood. 2012;120:2393.","journal-title":"Blood"},{"key":"789_CR29","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1073\/pnas.0607894104","volume":"104","author":"V Jankovic","year":"2007","unstructured":"Jankovic V, Ciarrocchi A, Boccuni P, DeBlasio T, Benezra R, Nimer SD. Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. Proc Natl Acad Sci U S A. 2007;104:1260\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"789_CR30","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1158\/1535-7163.MCT-13-0103-T","volume":"12","author":"H Mistry","year":"2013","unstructured":"Mistry H, Hsieh G, Buhrlage SJ, Huang M, Park E, Cuny GD, Galinsky I, Stone RM, Gray NS, D\u2019Andrea AD, Parmar K. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther. 2013;12:2651\u201362.","journal-title":"Mol Cancer Ther"},{"key":"789_CR31","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/sj.onc.1210676","volume":"27","author":"ZG Peng","year":"2008","unstructured":"Peng ZG, Zhou MY, Huang Y, Qiu JH, Wang LS, Liao SH, Dong S, Chen GQ. Physical and functional interaction of Runt-related protein 1 with hypoxia-inducible factor-1alpha. Oncogene. 2008;27:839\u201347.","journal-title":"Oncogene"},{"key":"789_CR32","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1158\/1535-7163.MCT-06-0526","volume":"6","author":"B Fu","year":"2007","unstructured":"Fu B, Xue J, Li Z, Shi X, Jiang BH, Fang J. Chrysin inhibits expression of hypoxia-inducible factor-1alpha through reducing hypoxia-inducible factor-1alpha stability and inhibiting its protein synthesis. Mol Cancer Ther. 2007;6:220\u20136.","journal-title":"Mol Cancer Ther"},{"key":"789_CR33","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1002\/ajh.24396","volume":"91","author":"MM Patnaik","year":"2016","unstructured":"Patnaik MM, Tefferi A. Chronic myelomonocytic leukemia: 2016 update on diagnosis, risk stratification, and management. Am J Hematol. 2016;91:631\u201342.","journal-title":"Am J Hematol"},{"key":"789_CR34","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/bjh.12756","volume":"165","author":"MM Patnaik","year":"2014","unstructured":"Patnaik MM, Parikh SA, Hanson CA, Tefferi A. Chronic myelomonocytic leukaemia: a concise clinical and pathophysiological review. Br J Haematol. 2014;165:273\u201386.","journal-title":"Br J Haematol"},{"key":"789_CR35","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/leu.2009.218","volume":"24","author":"N Carbuccia","year":"2010","unstructured":"Carbuccia N, Trouplin V, Gelsi-Boyer V, Murati A, Rocquain J, Adelaide J, Olschwang S, Xerri L, Vey N, Chaffanet M, et al. Mutual exclusion of ASXL1 and NPM1 mutations in a series of acute myeloid leukemias. Leukemia. 2010;24:469\u201373.","journal-title":"Leukemia"},{"key":"789_CR36","doi-asserted-by":"crossref","unstructured":"Su YJ, Kuo MC, Wang PN, Wu JH, Lin YH, Huang TY, Lin TL, Chang H, Hung YS, Shih LY. Genetic evolution patterns in patients with chronic myelomonocytic leukemia to secondary acute myeloid leukemia: an analysis of 36 paired samples. The 24th Congress of the European Hematology Association, Amsterdam, The Netherlands, June 13\u201316, 2019.","DOI":"10.1097\/02014419-201906001-00436"},{"key":"789_CR37","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1084\/jem.20171151","volume":"215","author":"R Nagase","year":"2018","unstructured":"Nagase R, Inoue D, Pastore A, Fujino T, Hou HA, Yamasaki N, Goyama S, Saika M, Kanai A, Sera Y, et al. Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation. J Exp Med. 2018;215:1729\u201347.","journal-title":"J Exp Med"},{"key":"789_CR38","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/jcb.22142","volume":"107","author":"AN Goldfarb","year":"2009","unstructured":"Goldfarb AN. Megakaryocytic programming by a transcriptional regulatory loop: a circle connecting RUNX1, GATA-1, and P-TEFb. J Cell Biochem. 2009;107:377\u201382.","journal-title":"J Cell Biochem"},{"key":"789_CR39","doi-asserted-by":"publisher","first-page":"5612","DOI":"10.1038\/onc.2008.175","volume":"27","author":"HC Suh","year":"2008","unstructured":"Suh HC, Leeanansaksiri W, Ji M, Klarmann KD, Renn K, Gooya J, Smith D, McNiece I, Lugthart S, Valk PJ, et al. Id1 immortalizes hematopoietic progenitors in vitro and promotes a myeloproliferative disease in vivo. Oncogene. 2008;27:5612\u201323.","journal-title":"Oncogene"},{"key":"789_CR40","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1182\/blood-2009-05-223115","volume":"114","author":"R Tang","year":"2009","unstructured":"Tang R, Hirsch P, Fava F, Lapusan S, Marzac C, Teyssandier I, Pardo J, Marie JP, Legrand O. High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia. Blood. 2009;114:2993\u20133000.","journal-title":"Blood"},{"key":"789_CR41","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1182\/blood-2015-03-635532","volume":"126","author":"L Wang","year":"2015","unstructured":"Wang L, Man N, Sun XJ, Tan Y, Garcia-Cao M, Liu F, Hatlen M, Xu H, Huang G, Mattlin M, et al. Regulation of AKT signaling by Id1 controls t (8;21) leukemia initiation and progression. Blood. 2015;126:640\u201350.","journal-title":"Blood"},{"key":"789_CR42","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1182\/blood-2009-06-229443","volume":"115","author":"MG Kharas","year":"2010","unstructured":"Kharas MG, Okabe R, Ganis JJ, Gozo M, Khandan T, Paktinat M, Gilliland DG, Gritsman K. Constitutively active AKT depletes hematopoietic stem cells and induces leukemia in mice. Blood. 2010;115:1406\u201315.","journal-title":"Blood"},{"key":"789_CR43","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.stem.2010.06.020","volume":"7","author":"K Takubo","year":"2010","unstructured":"Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M, Suda T, et al. Regulation of the HIF-1\u03b1 level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7:391\u201302.","journal-title":"Cell Stem Cell"},{"key":"789_CR44","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nrc1187","volume":"3","author":"GL Semenza","year":"2003","unstructured":"Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721\u201332.","journal-title":"Nat Rev Cancer"},{"key":"789_CR45","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1158\/1541-7786.MCR-06-0218","volume":"5","author":"HJ Kim","year":"2007","unstructured":"Kim HJ, Chung H, Yoo YG, Kim H, Lee JY, Lee MO, Kong G. Inhibitor of DNA binding 1 activates vascular endothelial growth factor through enhancing the stability and activity of hypoxia-inducible factor-1alpha. Mol Cancer Res. 2007;5:321\u20139.","journal-title":"Mol Cancer Res"},{"key":"789_CR46","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/359843a0","volume":"359","author":"D Shweiki","year":"1992","unstructured":"Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359:843\u20135.","journal-title":"Nature"},{"key":"789_CR47","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","volume":"16","author":"JA Forsythe","year":"1996","unstructured":"Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16:4604\u201313.","journal-title":"Mol Cell Biol"},{"key":"789_CR48","doi-asserted-by":"publisher","first-page":"6910","DOI":"10.1158\/1078-0432.CCR-06-0489","volume":"12","author":"TK Lee","year":"2006","unstructured":"Lee TK, Poon RT, Yuen AP, Ling MT, Wang XH, Wong YC, Guan XY, Man K, Tang ZY, Fan ST. Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1alpha-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma. Clin Cancer Res. 2006;12:6910\u20139.","journal-title":"Clin Cancer Res"},{"key":"789_CR49","doi-asserted-by":"publisher","first-page":"5198","DOI":"10.1038\/s41598-017-05564-x","volume":"7","author":"HS Youn","year":"2017","unstructured":"Youn HS, Kim TY, Park UH, Moon ST, An SJ, Lee YK, Hwang JT, Kim EJ, Um SJ. Asxl1 deficiency in embryonic fibroblasts leads to cellular senescence via impairment of the AKT-E2F pathway and Ezh2 inactivation. Sci Rep. 2017;7:5198.","journal-title":"Sci Rep"}],"container-title":["Journal of Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-019-0789-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13045-019-0789-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13045-019-0789-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T23:29:33Z","timestamp":1603236573000},"score":1,"resource":{"primary":{"URL":"https:\/\/jhoonline.biomedcentral.com\/articles\/10.1186\/s13045-019-0789-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,22]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["789"],"URL":"https:\/\/doi.org\/10.1186\/s13045-019-0789-3","relation":{},"ISSN":["1756-8722"],"issn-type":[{"value":"1756-8722","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,22]]},"assertion":[{"value":"10 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Ethics Committee of Chang Gung Memorial Hospital, and all experimental procedures have been done according to the institutional guidelines.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors reviewed and approved the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"104"}}