{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:53:13Z","timestamp":1791348793324,"version":"4.3.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,2,12]]},"abstract":"<jats:p>\n                    Acquisition of additional genetic and\/or epigenetic abnormalities other than the\n                    <jats:italic>BCR<\/jats:italic>\n                    \/\n                    <jats:italic>ABL<\/jats:italic>\n                    fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast crisis (BC). To gain insights into the underlying mechanisms of progression to BC, we screened DNA samples from CML patients during blast transformation for mutations in a number of transcription factor genes that are critical for myeloid\u2013lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of\n                    <jats:italic>GATA-2<\/jats:italic>\n                    , a negative regulator of hematopoietic stem\/progenitor cell differentiation. A L359V substitution within zinc finger domain (ZF) 2 of\n                    <jats:italic>GATA-2<\/jats:italic>\n                    was found in eight cases with myelomonoblastic features, whereas an in-frame deletion of 6 aa (\u0394341\u2013346) spanning the C-terminal border of ZF1 was detected in one patient at myeloid BC with eosinophilia. Further studies indicated that L359V not only increased transactivation activity of GATA-2 but also enhanced its inhibitory effects on the activity of PU.1, a major regulator of myelopoiesis. Consistent with the myelomonoblastic features of CML transformation with the\n                    <jats:italic>GATA-2<\/jats:italic>\n                    L359V mutant, transduction of the\n                    <jats:italic>GATA-2<\/jats:italic>\n                    L359V mutant into HL-60 cells or\n                    <jats:italic>BCR<\/jats:italic>\n                    \/\n                    <jats:italic>ABL<\/jats:italic>\n                    -harboring murine cells disturbed myelomonocytic differentiation\/proliferation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , respectively. These data strongly suggest that\n                    <jats:italic>GATA-2<\/jats:italic>\n                    mutations may play a role in acute myeloid transformation in a subset of CML patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0711824105","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T20:59:53Z","timestamp":1202158793000},"page":"2076-2081","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":166,"title":["Gain-of-function mutation of\n                    <i>GATA-2<\/i>\n                    in acute myeloid transformation of chronic myeloid leukemia"],"prefix":"10.1073","volume":"105","author":[{"given":"Su-Jiang","family":"Zhang","sequence":"first","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yuan","family":"Ma","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Li","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Dong","family":"Gao","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Cai","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Bao","family":"Ren","sequence":"additional","affiliation":[{"name":"Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South Street, Waltham, MA 02454-9110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Chen","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"},{"name":"Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai-Juan","family":"Chen","sequence":"additional","affiliation":[{"name":"*State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China;"},{"name":"Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,2,12]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-12-200612190-00008"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3656"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1633833100"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020777"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc989"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4111"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.14.6293"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.8.2013.bloodjournal8582013"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102583199"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205095"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.3.032802.115046"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.17.6783"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402062"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8705"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.5.2448"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00510-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00452-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.7.2375.bloodjournal8872375"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90277-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.20.6151"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4110"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.5.1933.h8001933_1933_1939"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207777"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00081-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1532\/IJH97.05051"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.4.1234.bloodjournal8841234"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510616103"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.569"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/85820"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.3.998"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.8.2543"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.2.706-715.2005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00056-X"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.7.2084"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3011"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206087"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.9.2722"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202619"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1598"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng791"},{"key":"e_1_3_3_41_2","first-page":"410","article-title":"Treatment of HL60 cells with various combinations of retinoids and 1\u03b1,25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis.","volume":"9","author":"Bunce CM","year":"1995","unstructured":"CM Bunce, LA Wallington, P Harrison, GR Williams, G Brown, Treatment of HL60 cells with various combinations of retinoids and 1\u03b1,25 dihydroxyvitamin D3 results in differentiation towards neutrophils or monocytes or a failure to differentiate and apoptosis. 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