{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:04:34Z","timestamp":1793361874935,"version":"4.5.0"},"reference-count":60,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>B-cell lymphoma 6 (BCL6) is a transcription repressor and proto-oncogene that plays a crucial role in the innate and adaptive immune system and lymphoid neoplasms. However, its role in myeloid malignancies remains unclear. Here, we explored the role of BCL6 in acute myeloid leukemia (AML). BCL6 was expressed at variable and often high levels in AML cell lines and primary AML samples. AMLs with higher levels of BCL6 were generally sensitive to treatment with BCL6 inhibitors, with the exception of those with monocytic differentiation. Gene expression profiling of AML cells treated with a BCL6 inhibitor revealed induction of BCL6-repressed target genes and transcriptional programs linked to DNA damage checkpoints and downregulation of stem cell genes. Ex vivo treatment of primary AML cells with BCL6 inhibitors induced apoptosis and decreased colony-forming capacity, which correlated with the levels of BCL6 expression. Importantly, inhibition or knockdown of BCL6 in primary AML cells resulted in a significant reduction of leukemia-initiating capacity in mice, suggesting ablation of leukemia repopulating cell functionality. In contrast, BCL6 knockout or inhibition did not suppress the function of normal hematopoietic stem cells. Treatment with cytarabine further induced BCL6 expression, and the levels of BCL6 induction were correlated with resistance to cytarabine. Treatment of AML patient-derived xenografts with BCL6 inhibitor plus cytarabine suggested enhanced antileukemia activity with this combination. Hence, pharmacologic inhibition of BCL6 might provide a novel therapeutic strategy for ablation of leukemia-repopulating cells and increased responsiveness to chemotherapy.<\/jats:p>","DOI":"10.1182\/blood.2019001745","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T17:59:16Z","timestamp":1599760756000},"page":"812-825","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["BCL6 maintains survival and self-renewal of primary human acute myeloid leukemia cells"],"prefix":"10.1182","volume":"137","author":[{"given":"Kimihito C.","family":"Kawabata","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Zong","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-6216","authenticated-orcid":false,"given":"Cem","family":"Meydan","sequence":"additional","affiliation":[{"name":"Institute for Computational Biomedicine and Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wyman","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas J.","family":"Wouters","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"},{"name":"Department of Hematology, Erasmus University Medical Center and Oncode Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-7154","authenticated-orcid":false,"given":"Mayumi","family":"Sugita","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinjoy","family":"Goswami","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Albert","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Yip","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0384-3658","authenticated-orcid":false,"given":"Gail J.","family":"Roboz","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengming","family":"Chen","sequence":"additional","affiliation":[{"name":"Healthcare Policy and Research, Weill Medical College of Cornell University, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud","family":"Delwel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus University Medical Center and Oncode Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-1642","authenticated-orcid":false,"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics,"},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine,"},{"name":"The WorldQuant Initiative for Quantitative Prediction, and"},{"name":"The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8074-2287","authenticated-orcid":false,"given":"Ari","family":"Melnick","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, 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