AsianScientist (Sep. 29, 2011) – People who study cancer or know someone who had cancer may know that low platelet numbers, or thrombocytopenia, are a side effect of chemotherapy.
The drop in the number of platelets – tiny cells that allow blood to clot – further diminishes the ability of patients to deal with even minor cuts. But why does this happen?
In a study published online in the Journal of Experimental Medicine, scientists at the Walter and Eliza Institute have answered an age-old question on the formation of platelets, and also why low platelet numbers are a side effect of chemotherapy.
Previously, it was thought that platelets formed through megakaryocytes in a process similar to cell death, through a process termed ‘shedding’ in which small fragments break off megakaryocytes (large cells normally found in the bone marrow).
But this does not appear to be the case at the molecular level.
“Our research tested this assumption by examining the molecules that are required for programmed cell death. We found that, at a molecular level, platelet formation does not occur by a death-like process,” said Dr. Emma Josefsson, lead author of the study.
Life-or-death decisions of cells are controlled by the Bcl-2 family of proteins. Some ‘pro-death’ Bcl-2 family proteins cause cells to die, while a ‘pro-survival’ faction prevents cell death, allowing cells to survive.
The team found that pro-death Bcl-2 family proteins were not required for platelet formation from megakaryocytes; in fact, the opposing pro-survival Bcl-2 family proteins were essential for keeping megakaryocytes alive so they could make platelets.
Chemotherapy was also shown to kill megakaryocytes by its action on Bcl-2 family proteins, which may help researchers develop new strategies to prevent chemotherapy-induced thrombocytopenia.
“Our work has shown that chemotherapy activates ‘pro-death’ Bcl-2 proteins to kill megakaryocytes, meaning patients are less capable of producing platelets as they recover from cancer treatment,” Dr. Josefsson said.
The article can be found at: Josefsson EC et al. (2011) Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets.
——
Source: The Walter and Eliza Hall Institute.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
#Australian Cancer Research Fund #Cancer Council Victoria #European Molecular Biology Organisation #Leukaemia Foundation of Australia #National Health and Medical Research Council Australia #Sylvia and Charles Viertel Charitable Foundation #The Walter and Eliza Hall Institute of Medical Research #University of Melbourne #Victorian Cancer Agency
