NUP98-HBO1-fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis.

ABSTRACT: Chronic myelomonocytic leukemia (CMML) constitutes a hematopoietic stem cell (HSC) disorder characterized by prominent monocytosis and myelodysplasia. Although genome sequencing has revealed the CMML mutation profile, the mechanism of disease development remains unclear. Here we show that aberrant histone acetylation by nucleoporin-98 (NUP98)-HBO1, a newly identified fusion in a patient with CMML, is sufficient to generate clinically relevant CMML pathogenesis. Overexpression of NUP98-HBO1 in murine HSC/progenitors (HSC/Ps) induced diverse CMML phenotypes, such as severe leukocytosis, increased CD115⁺ Ly6C^high monocytes (an equivalent subpopulation to human classical CD14⁺ CD16^- monocytes), macrocytic anemia, thrombocytopenia, megakaryocyte-linea

SUBMITTER: Hayashi Y 

PROVIDER: S-EPMC6457235 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature