Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.

Pathways defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Hematologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Hematology hsv//eng
Animals
Cell Transformation
Neoplastic
metabolism
pathology
Gene Expression Profiling
Gene Expression Regulation
Leukemic
Genes
Dominant
genetics
Granulocyte-Macrophage Progenitor Cells
metabolism
pathology
Homeodomain Proteins
metabolism
Humans
Leukemia
Myeloid
Acute
genetics
pathology
Mice
Mice
Inbred C57BL
Models
Biological
Multiprotein Complexes
metabolism
Neoplasm Proteins
metabolism
Promoter Regions
Genetic
genetics
Protein Binding
Tumor Suppressor Proteins
metabolism

Yun, Haiyang (author)
Berg, Tobias (author)
Yung, Eric (author)
Argiropoulos, Bob (author)
Kuchenbauer, Florian (author)
Park, Gyeongsin (author)
Hamwi, Iyas (author)
Palmqvist, Lars,1965Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xpalla (author)
Lai, Courteney K (author)
Leung, Malina (author)
Lin, Grace (author)
Chaturvedi, Anuhar (author)
Thakur, Basant Kumar (author)
Iwasaki, Masayuki (author)
Bilenky, Mikhail (author)
Thiessen, Nina (author)
Robertson, Gordon (author)
Hirst, Martin (author)
Kent, David (author)
Wilson, Nicola K (author)
Göttgens, Bertie (author)
Eaves, Connie (author)
Cleary, Michael L (author)
Marra, Marco (author)
Ganser, Arnold (author)
Humphries, R Keith (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin (creator_code:org_t)

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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