Brief report: Loss of p15Ink4b accelerates development of myeloid neoplasms in Nup98-HoxD13 transgenic mice.
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.
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Rita
R
Humeniuk
Richard
R
Koller
Juraj
J
Bies
Peter
P
Aplan
Linda
L
Wolff
D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D049109:Cell Proliferation; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000172:deficiency / Q000235:genetics*; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
D017252:CD3 Complex; C493968:Cdkn2b protein, mouse; D050762:Cyclin-Dependent Kinase Inhibitor p15; D018398:Homeodomain Proteins; C084118:Hoxd13 protein, mouse; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C093350:nuclear pore complex protein 98
Acute myelogenous leukemia; Myelodysplastic syndromes; Myeloproliferative disease; Nup98-HoxD13; Transgenic mouse; p15Ink4b