Myeloproliferative disease and myelodysplastic syndrome induced by transplantation of bone marrow cells expressing mutant p53.
p53 mutations are the most common genetic alterations observed in human cancers including lymphomas and leukemias. We have previously shown that transduction of normal murine hematopoietic cells with mutant p53 alone in vitro results in an enhanced proliferative capacity and modified differentiation potential of transduced cells. In order to investigate further the role of mutant p53 in hematopoietic cell transformation, mutant p53-transduced bone marrow cells were used to reconstitute the hematopoietic system of lethally irradiated mice. The results show that overexpression of mutant p53 can initiate the transformation of immature murine hematopoietic cells in vivo and induce two types of hematopoietic disorders, myeloproliferative disease and myelodysplastic syndrome.
Shounan
Y
Y
The RW Johnson Pharmaceutical Research Institute-Sydney, NSW, Australia.
MacKenzie
K
K
Dolnikov
A
A
Miller
M
M
Symonds
G
G
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D016159:Tumor Suppressor Protein p53