The laboratory has focused on two major areas of study. One area involves a determination of the mechanisms involved in development of promonocytic leukemia in our murine model. This disease is induced by a combination of Moloney MuLV or Amphotrophic MuLV and pristane. Our previous data had shown that c-myb activation by insertional mutagenesis in our model system occurs early in bone marrow and spleen within the first month following virus inoculation. This was determined using a sensitive RT-PCR technique to detect leukemia specific gag-myb mRNA. This year we determined that 1) cells undergoing c-myb activation during the preleukemic period can develop as separate clones at multiple bone marrow sites, 2) some mice that are resistant to disease are unable to support virus replication, as in the case of C57BL/6 mice. Alternatively mice of other resistant strains, for example NFS and C3HeJ, are able to support replication and support c-myb activation, but are blocked in tumor formation at a subsequent unknown step, 3) MuLVs that are nonpathogenic in susceptible strains of mice are capable of integrating at the c-myb locus and forming gag-myb mRNA through a splicing event identical to that utilized by Moloney MuLV; this suggests that, in mice infected with these viruses, the block to leukemia development also occurs at a late stage in the disease process. The second major area of study is one that was initiated this year and focuses on the structural-function relationships of the c-myb oncogene product. Sequences encoding mutated or variant forms of Myb protein analogous to the ones expressed in promonocytic tumors as well as the normal c-myb product have been placed in retroviruses vectors. These vectors have been shown to efficiently produce protein in transfected fibroblasts. Experiments aimed at determining the ability of these different forms of Myb to transform cells in vivo and block differentiation are underway.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB008952-07
Application #
3774351
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code