Krüppel-like factor 4 promotes survival and expansion in acute myeloid leukemia cells.

Autor:	Lewis AH; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Bridges CS; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Punia VS; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Cooper AFJ; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.; SMART Program at Baylor College of Medicine Houston, Houston, TX 77030, USA., Puppi M; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA., Lacorazza HD; Department of Pathology & Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2021 Feb 16; Vol. 12 (4), pp. 255-267. Date of Electronic Publication: 2021 Feb 16 (Print Publication: 2021).
DOI:	10.18632/oncotarget.27878
Abstrakt:	Acute myeloid leukemia (AML) is an aggressive hematological malignancy of the bone marrow that affects mostly elderly adults. Alternative therapies are needed for AML patients because the overall prognosis with current standard of care, high dose chemotherapy and allogeneic transplantation, remains poor due to the emergence of refractory and relapsed disease. Here, we found expression of the transcription factor KLF4 in AML cell lines is not silenced through KLF4 gene methylation nor via proteasomal degradation. The deletion of KLF4 by CRISPR-CAS9 technology reduced cell growth and increased apoptosis in both NB4 and MonoMac-6 cell lines. Chemical induced differentiation of gene edited NB4 and MonoMac6 cells with ATRA and PMA respectively increased apoptosis and altered expression of differentiating markers CD11b and CD14. Transplantation of NB4 and MonoMac-6 cells lacking KLF4 into NSG mice resulted in improved overall survival compared to the transplantation of parental cell lines. Finally, loss-of-KLF4 did not alter sensitivity of leukemic cells to the chemotherapeutic drugs daunorubicin and cytarabine. These results suggest that KLF4 expression supports AML cell growth and survival, and the identification and disruption of KLF4-regulated pathways could represent an adjuvant therapeutic approach to increase response. Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare. (Copyright: © 2021 Lewis et al.)
Databáze:	MEDLINE
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