JCI table of contents: Nov. 21, 2007( mailto:lpdubois@medecine.univ-mrs.fr lp...),Health

View the PDF of this article at: https://www.the-jci.org/article.php?id=32655

HEMATOLOGY: Two hits are better than one for causing leukemia

The genetic abnormalities that cause acute myeloid leukemia (AML) are many and varied. Although mice engineered to mimic a single genetic abnormality eventually develop leukemia, it is thought that a second genetic defect occurring as the mice age is required for this to happen. Support for this 2-hit hypothesis has now been generated by Pier Giuseppe Pelicci and colleagues from the European Institute of Oncology, Italy.

In this study, analysis of leukemic cells from individuals with AML indicated that disease associated with aberrant expression of the gene PRDM16 was accompanied by mutations in the gene that makes the p53 protein, which is known to suppress cancer development. Further analysis revealed that when one of the proteins made by the PRDM16 gene, sPRDM16, was overexpressed in the bone marrow of mice it could induce the development of leukemia, but the full extent of its leukemic potential required that the mice lack p53. These data led the authors to conclude that overexpression of sPRDM16 and disruption of the p53 tumor suppressor pathway cooperate in the development of leukemia, both in human patients with AML and in mice, and to suggest that inhibition of sPRDM16 is a potentially relevant antileukemogenic strategy.

TITLE: Overexpression of sPRDM16 coupled with loss of p53 induces myeloid leukemias in mice

AUTHOR CONTACT:

Pier Giuseppe Pelicci
European Institute of Oncology, Milan, Italy.
Phone: 39-02-57489868; Fax: 39-02-57489851; E-mail: piergiuseppe.pelicci@ifom-ieo-campus.it.

MEDIA CONTACT:

Donata
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