Insight

Rafael Fonseca: Multiple myeloma (MM) – subclonal, and not?

Photo of Rafael Fonseca taken from www.azbio.org

May 27, 2024, 08:13

Rafael Fonseca: Multiple myeloma (MM) – subclonal, and not?

Rafael Fonseca, Chief Innovation Officer at Mayo Clinic in Arizona, recently shared a post on X:

“Multiple myeloma (MM) – subclonal, and not?

After talking to some colleagues, it occurred to me that it’s worthwhile making a clarification about the subclonal nature of MM.

What does this mean?

It’s been 12 years since we published this paper with Jonathan Keats where DNA gain/loss (aCGH) was converted to FISH probes. Each pie represents the analysis of a unique bone marrow sample, over time, in the same patient.

Multiple subclones exist.

The pie charts show that cells are genetically different from each other. But by how much?

These subclones are almost identical to each other. It’s like those games that ask you to find 10 differences in pictures. Slightly different but mostly identical.

Rafael Fonseca: Multiple myeloma (MM) – subclonal, and not?

How did we know what genetic changes to track?- they don’t matter. They are just flags identifying subpopulations of cells. The size of the slice of the pie represents the fraction of cells with a given FISH abnormality.

Plasma cells in MM are always constant on two genetic things:

The DNA sequence of the B cell receptor- this is what we use to track MRD with clonoSEQ
Primary genetic changes, like translocations

100% of cells have the same sequence and translocations – forever.

I call these changes the ‘soul of the cell’.

I use the graph below to identify the same subclones, but now with a black spot in the center. This dot represents the primary genetic abnormalities and the sequence of the B-cell receptor.

This never changes!”