This is a follow up to Prognostic Indicators (Part 1) that should be reviewed first.
Take Away Points:
- There has been an explosion of new prognostic indicators (also called prognostic markers) in the last few years.
- Many of these are mutated genes that are not picked up by FISH or other routine testing. (This has nothing to due with our “mutation” status)
- These newer prognostic markers help explain some of the widely different outcomes in patients with similar FISH and mutation status.
- How they will impact clinical care is yet undetermined.
- NOTCH1 is commonly seen with unmutated trisomy 12 and is associated with poorer outcomes.
- BIRC3 is associated with Fludarabine resistance.
- FBXW7 and SF3B1 are new negative markers
- P53 and ATM, although usually associated with 17p and 11q deletions respectively can occur independently
- Complex Karyotype is an indicator of genomic instability associated with poor outcomes in several clinical settings.
New Prognostic Indicators:
In an effort to better predict how well we will do with our CLL and with the advent of next generation deep sequencing of our cancer gene, we have discovered a host of new ways our clone can misbehave at the genetic level, turning on and off various processes that might support cancer growth, inhibit death signals, and prevent suicide of damaged cells.
My friend, fellow blogger, and CLL researcher, Dr. Jeff Sharman has written an excellent overview of some on the major next generation CLL prognosis indicator. While the list is hardy exhaustive or final, it is a great start to understanding some of this latest research.
One that didn’t make his list was the poorer outcomes associated with a complex karyotype. This is a different type of marker, found by another type of lab test that involves looking at the chromosomes of our clone and checking for the presence of three of more distinct abnormalities. Think of it as a marker of genetic instability and an increased ability and tolerance of spawning mutant and sometime resistant offspring.
Here is the link to Dr. Sharman’s blog post on newer prognostic indicators.
New algorithms incorporating the mixes of old and new markers are constantly being developed that will may help better prognosticate and perhaps even guide therapy.
The only certainty is that we are not nearly finished with the search. We will be continuing to uncover critically damaged or missing genes and the proteins they produce and other as yet undiscovered prognostic indicators.
Brian Koffman 2/26/15