Mutated NPM1 in combination with overexpression of Meis1 or Hoxa9 is not sufficient to induce acute myeloid leukemia

Hanna Grauers Wiktorin; Tina Nilsson; Ann Jansson; Lars Palmqvist; Anna Martner

doi:10.1186/s40164-016-0053-2

Mutated NPM1 in combination with overexpression of Meis1 or Hoxa9 is not sufficient to induce acute myeloid leukemia

Exp Hematol Oncol. 2016 Aug 11:5:25. doi: 10.1186/s40164-016-0053-2. eCollection 2015.

Authors

Hanna Grauers Wiktorin¹, Tina Nilsson², Ann Jansson², Lars Palmqvist^#^{2

3}, Anna Martner^#¹

Affiliations

¹ Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, 413 45 Gothenburg, Sweden.
³ Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

^# Contributed equally.

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.

Aim: 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.

Findings and conclusion: 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.

Keywords: Acute myeloid leukemia; Hoxa9; Meis1; NPM1.