MicroRNA-155 is upregulated in MLL-rearranged AML but its absence does not affect leukemia development.
MicroRNA-155 (miR-155) is an oncogenic miRNA upregulated in various tumor types and leukemias and has been suggested as a potential drug target. Based on our previous work detecting high miR-155 levels in response to Meis1 overexpression in a murine Hox leukemia model, we show here the relationship among HOXA9, MEIS1, and miR-155 levels in MLL-translocated acute myeloid leukemia (AML) patients. Using mouse bone marrow cells transformed by MLL-fusion genes expressing graduated levels of Meis1, we show a positive correlation between miR-155 and Meis1. However, using a miR-155-knockout mouse model, we show that the absence and the depletion of miR-155 have no effect on leukemia formation or progression. We also show for the first time that miR-155 levels are correlated with MLL translocations, but that miR-155 expression is dispensable for the formation of AML and has no effect on leukemia progression.
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Edith
E
Schneider
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
Anna
A
Staffas
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Linda
L
Röhner
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Kathrin
K
Krowiorz
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Michael
M
Heuser
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Konstanze
K
Döhner
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Lars
L
Bullinger
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Hartmut
H
Döhner
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
Linda
L
Fogelstrand
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Arefeh
A
Rouhi
Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany. Electronic address: florian.kuchenbauer@uni-ulm.de.
Florian
F
Kuchenbauer
Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: lars.palmqvist@clinchem.gu.se.
Lars
L
Palmqvist
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D055786:Gene Knockout Techniques; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion
D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C524942:MIRN155 microRNA, human; C000616392:Meis1 protein, mouse; D035683:MicroRNAs; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C097899:homeobox protein HOXA9; D051788:Myeloid-Lymphoid Leukemia Protein