Open AccessBrief Report: Loss of p15Ink4b Accelerates Development of Myeloid Neoplasms in Nup98‐HoxD13 Transgenic Mice
Author(s) -
Humeniuk Rita,
Koller Richard,
Bies Juraj,
Aplan Peter,
Wolff Linda
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1635
Subject(s) - biology , myelodysplastic syndromes , myeloid , myeloid leukemia , progenitor cell , haematopoiesis , cancer research , stem cell , leukemia , immunology , carcinogenesis , progenitor , bone marrow , cancer , microbiology and biotechnology , genetics
Homeostasis of hematopoietic stem and progenitor cells is a tightly regulated process. The disturbance of the balance in the hematopoietic progenitor pool can result in favorable conditions for development of diseases such as myelodysplastic syndromes and leukemia. It has been shown recently that mice lacking p15Ink4b have skewed differentiation of common myeloid progenitors toward the myeloid lineage at the expense of erythroid progenitors. The lack of p15INK4B expression in human leukemic blasts has been linked to poor prognosis and increased risk of myelodysplastic syndromes transformation to acute myeloid leukemia. However, the role of p15Ink4b in disease development is just beginning to be elucidated. This study examines the collaboration of the loss of p15Ink4b with Nup98‐HoxD13 translocation in the development of hematological malignancies in a mouse model. Here, we report that loss of p15Ink4b collaborates with Nup98‐HoxD13 transgene in the development of predominantly myeloid neoplasms, namely acute myeloid leukemia, myeloproliferative disease, and myelodysplastic syndromes. This mouse model could be a very valuable tool for studying p15Ink4b function in tumorigenesis as well as preclinical drug testing. S tem C ells 2014;32:1361–1366