The key role of a protein in a form of leukemia

An investigation reveals the important role of a protein in the development of chronic myelogenous leukemia.

A team of researchers led by the Higher Council for Scientific Research (CSIC) in Spain has discovered that the SOS1 protein is necessary to develop chronic myelogenous leukemia, a type of cancer in which the bone marrow produces too many white blood cells. This finding offers a novel way to design new drugs that could be useful in cases of resistance to chronic treatments such as Imatinib or other tyrosine kinase inhibitors.

Most people with CML, 90%, have a genetic mutation called the Philadelphia chromosome. A section of chromosome 9 (ABL) and a section of chromosome 22 (BCR) break off and switch places. The BCR-ABL gene forms on chromosome 22, where it attaches to a section of chromosome 9, and this altered chromosome 22 is called the Philadelphia chromosome. Previous work carried out in vitro and in vivo by the group led by Eugenio Santos at the Salamanca Cancer Research Center (CIC), a joint institute of the CSIC and the University of Salamanca, had demonstrated the relevance of the SOS family of proteins in the development of skin cancer and other studies had linked the SOS1 protein with leukemogenesis mediated by the BCR-ABL gene.

In this new research, a murine model has been used in which the animals are carriers of the p210BCR/ABL oncoprotein and deficient in the expression of SOS proteins. “Our data show that direct gene ablation of SOS1 results in significant suppression of all typical pathological features of CML, such as peripheral blood leukocyte count and bone marrow hematopoietic stem cell formation capacity, which shows that the deficiency of this protein protects against the development of the disease”, explains Santos, a scientist at the CIC and the Cancer Network Biomedical Research Center (CIBERONC) in Spain.

Granulocytes in blood samples from mice with chronic myelogenous leukemia. (Photo: CSIC)

The results of the new research add to the growing body of evidence that inhibition of SOS1 would be a good therapeutic approach for treating cancer.

The study is titled “Critical Requirement of SOS1 for Development of BCR/ABL-Driven Chronic Myelogenous Leukemia.” And it has been published in the academic journal Cancers. (Source: CIC / CSIC)