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Clonal Heterogeneity In CLL: Part 1

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Take Away Points:

  • Cancer by its nature is genomic unstable.
  • Over time it acquires more mutations.
  • New clones and sub-clones can arise over time.
  • Therapy can influence the balance and evolution of the clonal and sub-clonal populations.


Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting.  With time and experience, you’ll become familiar with the terminology and acronyms.  We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We will also provide a glossary for your reference.

To enjoy the most benefit from this article, it is best to be already familiar with the subjects covered in prognostic marker Part 1 and Part 2.

Clonal Heterogeneity:

Dr. Cathy Wu out of Dana-Farber starts at the basics.

In the first of our two part interview from the International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment in Greece in November 2014 she reminds us that while the concept that any cancer is made of multiple populations of different cells dates back to the 70s, it is our recent ability to look deeply and quickly at the genome with next generation genetic sequencing that has really cracked open our understanding of how huge a factor this is in one’s particular CLL aggressiveness and its ability to become resistance to therapy.

We now know that questions about the presence or absence of a good or bad prognostic indicators often should not be answered with a simple yes or no.

More importantly we know that our population of our cancer cells evolves over time. Hence the need to repeat FISH and other tests when the contemplating therapy.

An analogy: In most good movies the lead protagonist has an arc to his or her character. We see how he or she changes and evolves in response to the support received or the challenges faced.

So too it is with our cancer. Unfortunately CLL is much more like a movie than a snapshot. Dr. Wu explains our cancer may evolve over time in response to therapy and other selection pressures.

Please enjoy our video interview with Dr. Cathy Wu.

If you want to dig deep, take a look at this Blood Journal abstract or this abstract from ASH 2014 or this older full text from the Journal of Clinical Oncology or this on the evolution of resistance to BTK inhibitors such as ibrutinib as just a few of the many examples of the explosion of research in this field.

Our understanding of this complicated concept is itself evolving.

I believe it is extremely important stuff with enormous implications for how we should treat our cancer.

We deal with that and more in the second and final segment of this interview.

Brian Koffman 3/10/15