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Linkage of Meis1 le...
Linkage of Meis1 leukemogenic activity to multiple downstream effectors including Trib2 and Ccl3.
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Argiropoulos, Bob (author)
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- Palmqvist, Lars, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Yung, Eric (author)
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Kuchenbauer, Florian (author)
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Heuser, Michael (author)
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Sly, Laura M (author)
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Wan, Adrian (author)
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Krystal, Gerald (author)
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Humphries, R Keith (author)
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(creator_code:org_t)
- Elsevier BV, 2008
- 2008
- English.
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In: Experimental hematology. - : Elsevier BV. - 0301-472X. ; 36:7, s. 845-59
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- OBJECTIVE: MEIS1, a HOX cofactor, collaborates with multiple HOX and NUP98-HOX fusion proteins to accelerate the onset of acute myeloid leukemia (AML) through largely unknown molecular mechanisms. MATERIALS AND METHODS: To further resolve these mechanisms, we conducted a structure-function analysis of MEIS1 and gene-expression profiling, in the context of NUP98-HOXD13 (ND13) leukemogenesis. RESULTS: We show, in a murine bone marrow transplantation model, that the PBX-interaction domain, the homeodomain, and the C-terminal domain of MEIS1, are all required for leukemogenic collaboration with ND13. In contrast, the N-terminal domain of MEIS1 is dispensable for collaboration with ND13, but is required for Flt3 upregulation, indicating additional roles for MEIS1 in induction of leukemia independent of alterations in Flt3 expression. Gene-expression profiling of a cloned ND13 preleukemic cell line transduced with wild-type or Meis1 mutant forms revealed deregulation of multiple genes, including a set not previously implicated as MEIS1 targets. Chromatin immunoprecipitation revealed the in vivo occupancy of MEIS1 on regulatory sequences of Trib2, Flt3, Dlk1, Ccl3, Ccl4, Pf4, and Rgs1. Furthermore, engineered overexpression of Trib2 complements ND13 to induce AML while Ccl3 potentiates the repopulating ability of ND13. CONCLUSION: This study shows that Meis1-induced leukemogenesis with ND13 can occur in the absence of Flt3 upregulation and reveals the existence of other pathways activated by MEIS1 to promote leukemia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Animals
- Bone Marrow Transplantation
- Cell Line
- Tumor
- Cell Transformation
- Neoplastic
- genetics
- metabolism
- Chemokine CCL3
- biosynthesis
- genetics
- Disease Models
- Animal
- Gene Expression Profiling
- Gene Expression Regulation
- Leukemic
- genetics
- Genetic Complementation Test
- Homeodomain Proteins
- biosynthesis
- genetics
- Intracellular Signaling Peptides and Proteins
- genetics
- Leukemia
- Myeloid
- Acute
- genetics
- metabolism
- Linkage (Genetics)
- Mice
- Neoplasm Proteins
- biosynthesis
- genetics
- Oncogene Proteins
- Fusion
- genetics
- metabolism
- Protein Structure
- Tertiary
- genetics
- Protein-Serine-Threonine Kinases
- biosynthesis
- genetics
- Response Elements
- genetics
- Retroviridae
- Structure-Activity Relationship
- Transduction
- Genetic
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Argiropoulos, Bo ...
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Palmqvist, Lars, ...
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Yung, Eric
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Kuchenbauer, Flo ...
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Heuser, Michael
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Sly, Laura M
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show more...
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Wan, Adrian
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Krystal, Gerald
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Humphries, R Kei ...
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show less...
- 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 Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Experimental hem ...
- By the university
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University of Gothenburg