title: Mutated NPM1 in combination with overexpression of Meis1 or Hoxa9 is not sufficient to induce acute myeloid leukemia.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) carrying nucleophosmin 1 (NPM1) mutations (NPMc(+)) is regarded as a separate entity of myeloid neoplasms due to its distinct biological and clinical features. However, NPMc(+) alone displays low leukemogenic activity and cooperating events appear crucial for AML to develop. Dysregulation of homeobox genes, such as HOXA9 and MEIS1, is a common transcriptional signature of NPMc(+) AML. Furthermore, the pathogenic role for NPMc(+) in AML remains incompletely understood.
  
  
  OBJECTIVE
  To elucidate if NPMc(+) collaborates with Meis1 or Hoxa9 in the evolvement of AML.
  
  
  METHODS
  Murine bone marrow cells were genetically engineered to express mutated NPM1 variant A in combination with overexpression of Meis1 or Hoxa9. The capacity of the transduced cells to transform in vitro and to cause leukemia in vivo was then assessed.
  
  
  CONCLUSIONS
  There was no synergy between NPMc(+) and Meis1 or Hoxa9 in causing leukemogenic transformation of murine bone marrow cells, or in inducing AML in a transplantation model. Hence, overexpression of Meis1 or Hoxa9 in combination with NPMc(+) expression was not sufficient to generate an NPMc(+) AML mouse model.
authors.affiliation: Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hanna Grauers
authors.initials: HG
authors.lastname: Wiktorin
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, 413 45 Gothenburg, Sweden.
authors.forename: Tina
authors.initials: T
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, 413 45 Gothenburg, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Jansson
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, 413 45 Gothenburg, Sweden.|Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.identifier: 0000-0001-9274-360X
authors.initials: L
authors.lastname: Palmqvist
authors.affiliation: Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Martner
keywords: Acute myeloid leukemia; Hoxa9; Meis1; NPM1