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Tyrosine kinase inhibitors (TKIs) imatinib and its derivatives represent a breakthrough for CML therapy, but the use of TKI alone is ineffective for many CML patients. CD69, an early activation marker of lymphocytes, participates in immune and inflammatory responses. Previous studies revealed that BCR\u2010ABL upregulates CD69 expression; however, the role of CD69 in CML cells is unknown. Here, we demonstrate that BCR\u2010ABL induced CD69 promoter activity and mRNA and protein expression via the NF\u2010\u03baB pathway. CD69 knockdown partially increased apoptosis and expression of erythroid differentiation markers, \u03b1\u2010globin, \u03b6\u2010globin, and glycophorin A, and increased imatinib sensitivity in K562 and KU812 CML cells. Gene microarray analysis and quantitative real\u2010time PCR verified that CD24, an oncogenic gene, downregulated in K562 cells upon CD69 knockdown. CD69 overexpression increased, whereas CD69 knockdown inhibited CD24 promoter activity and mRNA and protein levels. CD24 knockdown also partially increased apoptosis, erythroid differentiation, and imatinib sensitivity in K562 cells, whereas its overexpression inhibited the effects of CD69 knockdown on apoptosis, erythroid differentiation, and imatinib sensitivity in K562 cells. Imatinib\u2010induced apoptosis and erythroid differentiation were also inhibited by CD69 or CD24 overexpression in BCR\u2010ABL\u2010expressing CML cell lines and CD34\n                      <jats:sup>+<\/jats:sup>\n                      cells. Taken together, CD24 is a downstream effector of CD69. CD69 and CD24 partially inhibit apoptosis and erythroid differentiation in CML cells; thus, they may be potential targets to increase imatinib sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26599","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:03:02Z","timestamp":1523923382000},"page":"7467-7479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CD69 partially inhibits apoptosis and erythroid differentiation via CD24, and their knockdown increase imatinib sensitivity in BCR\u2010ABL\u2010positive cells"],"prefix":"10.1002","volume":"233","author":[{"given":"Shih\u2010Yun","family":"Huang","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hsiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Yen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5553-112X","authenticated-orcid":false,"given":"Huei\u2010Mei","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11507"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646837"},{"key":"e_1_2_7_4_1","first-page":"995","article-title":"CD69 expression in B\u2010cell chronic lymphocytic leukemia: A new prognostic marker","volume":"86","author":"D'Arena G.","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00348-14"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.052829"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021337"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609567200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000140633"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.07.006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2017.05.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2008.07.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20942"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21627"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1871"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.03.006"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08800.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.36"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2756"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600702"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139112"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061939"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-273987"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1357"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212278200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.37.21545"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8489"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/7.8.1193"},{"key":"e_1_2_7_29_1","first-page":"2394","article-title":"Knockdown of CD24 inhibits proliferation, invasion and sensitizes breast cancer MCF\u20107 cells to tamoxifen in vitro","volume":"19","author":"Ma Z. 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