One of these types of genetic mutations is called a gain of 1q, or three or more extra copies of the 1q chromosome. If there are four or more copies of the 1q chromosome, it is considered to be a high risk feature and patients don't live as long as other types of myeloma. 
 
Dutch researchers have found that multiple myeloma with the 1q gain may respond to an MCL-1 inhibitor called S63845 by testing it in 31 human myeloma cell lines and in 47 bone marrow biopsy samples from myeloma patients. For the first time, they found that myeloma patients with the 1q gain (or amplification) are significantly more sensitive to the inhibition of MCL-1. They also found that having high beta-2 microglobulin and having kidney issues also correlated with increased sensitivity to MCL-1 inhibitor treatment. 
 
MCL-1 is a protein that is made from the MCL gene and it belongs to the Bcl-2 family. If this gene is mutated, then it can stop cancer cells from dying when they should. This prosurvival mechanism commonly occurs in blood cancers, including multiple myeloma. Because MCL1 is one of the genes located on 1q21, the researchers hypothesized that amplification of 1q21 would lead to increased MCL-1 expression and make MCL-1 easier to target.
 
The researchers tested all samples with three types of therapy: 1) S63845 (the MCL-inhibitor), 2) Venetoclax (a Bcl-2 inhibitor) and 3) A-1331852 (a BCL-XLi inhibitor). They tested them alone and then in combination. When used alone, the S63845 killed the most myeloma cells compared to the other two treatments. This indicated that the 1q gain myeloma was particularly solely dependent on MCL-1 expression for survival.