Lab tests point to better outcome for human blood cancers

The treatment of a range of human blood cancers, such as chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, may be improved as a result of international research involving The University of Western Australia (UWA).

An analysis of the work by Research Professor Wally Langdon and Assistant Professor Christine Thien at UWA’s School of Pathology and Laboratory Medicine and researchers at Yale University School of Medicine in the US is published in the journal Cancer Cell.

Professors Langdon and Thien produced genetically modified mice with a mutation in the c-Cbl gene and found that these mice develop a lethal myeloid leukemia. c-Cbl is a cancer-causing gene discovered by Professor Langdon that is mutated in some human blood cancers.

“These mice provide a preclinical model for studying human leukemias with c-Cbl mutations,” Professor Langdon said. “We are currently using these mice to identify anti-cancer drugs that will be effective for treating c-Cbl-associated leukemias.

“We found that mice with a c-Cbl mutation have enhanced activity of a growth factor receptor called FLT3 which is expressed on undifferentiated blood cells known as multipotent progenitors (MPPs). A consequence of this enhanced activity is a marked increase in the numbers of MPPs in the bone marrow of c-Cbl-mutant mice.

“This finding prompted us to generate c-Cbl-mutant mice with an additional mutation that deleted the gene for the growth factor that binds to and activates FLT3. Remarkably, by deleting this growth factor we completely blocked the expansion of MPPs and prevented the development of leukemia.”

Professor Langdon said the finding was significant as it indicates that leukemia patients with c-Cbl mutations would benefit from treatment with drugs that specifically target FLT3 and block its activity.