A fetal tumor suppressor axis abrogates MLL-fusion-driven acute myeloid leukemia.

Autor:	Eldeeb M; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Yuan O; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Guzzi N; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Thi Ngoc PC; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Konturek-Ciesla A; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Kristiansen TA; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Muthukumar S; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Magee J; Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA., Bellodi C; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Yuan J; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden., Bryder D; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medical, Lund University, 221 84 Lund, Sweden. Electronic address: david.bryder@med.lu.se.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112099. Date of Electronic Publication: 2023 Feb 09.
DOI:	10.1016/j.celrep.2023.112099
Abstrakt:	MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. Mechanistically, LIN28B directly binds to MYBBP1A mRNA, resulting in elevated protein levels of this MYB co-repressor. Functionally, overexpression of MYBBP1A phenocopies the tumor-suppressor effects of LIN28B, while its perturbation omits it. Thereby, we propose that developmentally restricted expression of LIN28B provides a layer of protection against MYB-dependent AML. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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