Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma
Blood Advances, American Society of Hematology
Primary author: Mauricio Zangari, M.D.
The minimal residual disease (MRD) test can identify myeloma in the bone marrow of patients in remission by standard criteria. This research describes 568 patients who achieved MRD negativity after autologous stem cell transplant. With a follow-up of nearly 10 years, 61% of patients remained MRD negative after stem cell transplant, while 39% became MRD positive at six years, with the highest risk of MRD conversion five years after treatment. MRD conversion was linked to increased risk of relapse. Importantly, not all MRD positive patients experienced a relapse, and 27% of positive patients had not relapsed at 10 years. MRD conversion from negative to positive correctly predicted relapse in 70% of patients. This study demonstrates the benefits of continued MRD assessment.
TRIP13 modulates protein de-ubiquitination and accelerates tumor development and progression of B cell malignancies
The Journal of Clinical Investigation
June 1, 2021
Primary author: Can Li, Ph.D.
The carefully orchestrated abundance of proteins within a cell controls cell proliferation. Proteasome inhibitors act as anti-myeloma agents by disabling the machine that degrades cellular proteins tagged with a molecule called ubiquitin. The increased ubiquinated protein levels within the tumor cell causes stress-induced cell death. The removal of the ubiquitin “tag” from cellular proteins, a process termed “deubiquitination,” can also increase protein stability. Research at UAMS identified TRIP13 as a gene abnormally overexpressed in high-risk myeloma. The research also noted that TRIP13 causes resistance to proteasome inhibitors, and that the tumor promoting activity of TRIP13 can be overcome by inhibiting deubiquitinase, called USP7. The data point to the central importance of protein stability in cancer biology and that targeting ubiquitination of proteins may complement the already established anti-myeloma effects of proteasome inhibition therapy.