The importance of Mcl-1 lies in the differing roles it plays in health and disease.
"On one hand, this protein keeps HSCs and progenitor cells alive and multiplying so the body can maintain its needed supply of blood cells," he said. "However, Mcl-1 also prevents the abnormal white blood cells found in leukemia from undergoing apoptosis in response to chemotherapy or radiation. This makes the leukemia cells resistant to treatments designed to damage the cell so it undergoes apoptosis." Opferman is continuing his studies of Mcl-1 at St. Jude to better understand the role this protein plays in both normal hematopoiesis (production of blood cells) as well as in potentially fatal blood cancers.
Opferman and his colleagues had previously shown that Mcl-1 is needed to ensure that HSCs and progenitor cells produced by HSCs are able to generate more specific cells, such as the immune cells known as B and T lymphocytes.
In the Science study, Opferman's team genetically modified mice so that the gene for Mcl-1 could be specifically deleted from the genome of HSCs and progenitor cells. Upon genetic deletion, these mice developed anemia and had severely reduced numbers of bone marrow (BM) cells, such as HSCs and progenitor cells. This was strong evidence that Mcl-1 was needed to maintain these cell populations.
The team also demonstrated that BM cells lacking Mcl-1 did not multiply when removed from mice and cultured in the laboratory. However, BM cells with the gene continued to flourish. In contrast, liver cells were unaffected following loss of Mcl-1, demonstrating that Mcl-1 is important only in certain cell types. Fina
Source:St. Jude Children's Research Hospital