Scientists have developed a novel mouse model for leukemia that reveals critical information about the mechanisms involved in leukemia progression and provides a model system for evaluation of new drugs for treatment of leukemia. The research, published in the January issue of Cancer Cell, utilizes a technique that allows induction and study of a key oncoprotein in adult mice. Previously, it was difficult to investigate this oncoprotein in the mouse, as the expression of this gene is associated with embryonic lethality, or death of the developing mouse in utero.
Acute myeloid leukemia (AML) can arise from genetic alterations in the bone marrow cells that give rise to blood cells. One fusion oncoprotein that is present in about 12% of human AML cases and is known to interfere with the process of normal blood cell development is called CBFB-SMMHC. Thus far, this protein has been very difficult to study in mouse models, as its expression causes embryonic lethality. Dr. Lucio H. Castilla from the Program in Gene Function and Expression at the University of Massachusetts Medical School and colleagues created a conditional mouse model to analyze the preleukemic effects of CBFB-SMMHC on blood cell production and AML development in adult mice. The mouse model enabled the scientists to selectively turn on expression of CBFB-SMMHC in adult mice, thereby avoiding embryonic lethality of expression of this gene, and then study the effects.
The researchers found that CBFB-SMMHC induction was associated with a reduction of immature blood cells in the bone marrow and with the appearance of abnormal progenitor cells that are leukemic precursors. Mice expressing CBFB-SMMHC developed AML with a median latency of approximately five months, with the time of disease onset varying with the number of abnormal cells in the bone marrow. Interestingly, additional studies showed that the blood stem cell precursors that expressed CBFB-SMMHC were maintained at normal levels for long periods of time, but their ability to differentiate into multiple types of blood cells was severely compromised.
Heidi Hardman | EurekAlert!
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