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A fetal tumor suppr...
A fetal tumor suppressor axis abrogates MLL-fusion-driven acute myeloid leukemia
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- Eldeeb, Mohamed (author)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Yuan, Ouyang (author)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Guzzi, Nicola (author)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine
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- Thi Ngoc, Phuong Cao (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Konturek-Ciesla, Anna (author)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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- Kristiansen, Trine A. (author)
- Lund University,Lunds universitet,Utvecklingsimmunologi,Forskargrupper vid Lunds universitet,Developmental Immunology,Lund University Research Groups
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- Muthukumar, Sowndarya (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Magee, Jeffrey (author)
- Washington University in St. Louis
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- Bellodi, Cristian (author)
- Lund University,Lunds universitet,RNA och stamcellsbiologi,Forskargrupper vid Lunds universitet,RNA and Stem Cell Biology,Lund University Research Groups
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- Yuan, Joan (author)
- Lund University,Lunds universitet,Utvecklingsimmunologi,Forskargrupper vid Lunds universitet,Developmental Immunology,Lund University Research Groups
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- Bryder, David (author)
- Lund University,Lunds universitet,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Developmental Hematopoiesis,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 42:2
- Related links:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- AML
- CP: Cancer
- hematopoiesis
- leukemia-initiating cell
- LIN28B
- MLL-rearrangements
- MYB
- MYBBP1A
- ontogeny
- tumor suppression
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Eldeeb, Mohamed
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Yuan, Ouyang
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Guzzi, Nicola
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Thi Ngoc, Phuong ...
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Konturek-Ciesla, ...
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Kristiansen, Tri ...
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Muthukumar, Sown ...
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Magee, Jeffrey
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Bellodi, Cristia ...
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Yuan, Joan
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Bryder, David
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cell Reports
- By the university
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Lund University