Week 10

Hi everyone!

I can’t believe it’s been 10 weeks already! Luckily, it looks like I’m just about finished putting together the results for my project.

On Monday, I received my first set of patient samples. These samples came from a single patient at 3 distinct timepoints. Although they were collected as bone marrow samples, I only worked with the extracted DNA leftover from when our lab had sent these samples out for sequencing. To understand what information we can gain from these samples, we first need to know what makes these samples different.

The first sample was collected very early in the disease’s progression, called smoldering multiple myeloma. I was surprised to learn that the distinction between SMM, the preceding stage (called monoclonal gammopathy of undetermined significance, or MGUS), and full blown multiple myeloma is actually based solely on a few ratios. The difference between a MGUS, a pre-clinical condition that requires no treatment and only semi-annual blood tests for monitoring, and SMM, a condition usually treated aggressively via a combination of a bone marrow transplant and several drugs, is based only on whether a bone marrow sample contains more or less than 10% plasma cells.

The distinction between multiple myeloma and MGUS/SMM, however, is much clearer. By time the disease has progressed to MM, the malignant plasma cells have displaced far more cells in the bone marrow. Therefore, while the first sample I’m working with consists largely of healthy cells normally found in bone marrow along with some tumor cells, the second sample I have is predominantly myeloma cells.

The final sample I have was collected after treatment with a combination therapy of two drugs. Because these therapies have killed off many of the myeloma cells in the bone marrow, the final bone marrow sample may have even less myeloma cells than the original SMM sample. That doesn’t mean the therapy will be effective long-term, though, because these surviving cells may be different from the original population of tumor cells in the SMM bone marrow. Recent studies show this actually occurs through natural selection—one cell in the initial SMM population gets a mutation that lets it reproduce more rapidly, leading to it overtaking the growth of other tumor cells in the initial population.

Our goal is essentially to determine what mutations are found in the full-blown MM sample but not the other two—and as soon as I get the sequencing data back for these samples, I’ll be able to design a qPCR assay that will help us in better detecting these differences.

Even though the progress I’ve made is far from revolutionary, I’m incredibly glad to see how much I’ve learned since my first day in the lab. I’m excited to see the other ways I’ll be able to apply this assay (and the other projects I will be involved with) throughout the summer! Thank you all for following my project!