Sunday, March 15, 2015

ESH 2014: Dr. Cathy Wu Explains TUMOR HETEROGENEITY and CLONAL EVOLUTION in CLL (Chronic Lymphocytic Leukemia)

This is taken from the first of a two part interview with Dr. Cathy Wu in Greece where I spoke on the patients' perspective at a meeting of the Greek Hematology Professional Congress.

It is also a teaser of what is to come in the new website of the nonprofit The CLL Society. That CLL specific education and support site should launch in the next few weeks. It will offer much deeper and broader information and be more searchable than is possible with a blog. 

Be assured that my blog is not going away but may revert back to more of a personal blog and the place where I continue to host my candid and occasionally combative opinions and commentaries. 

Truth is that the plethora of news and emerging therapies in CLL have outgrown the capacity of my time linear blog to keep up. This new format also will offer the chances to hear other patient voices in what will be the only patient driven physician curated place on the web for CLL support and education.

I and the team of fellow volunteers are pretty excited. It's been a ton of work, but our mission is to address the unmet needs of the CLL community and we believe this new website will be a helpful piece of that effort. There is great information out there and we want to help everyone find it and explain it in our soon to be born strong and friendly CLL focused website.

Honestly, my efforts to help launch our nonprofit 510c3 and its website has consumed me, leaving less time to post here.

While we are still building phase 1 of the new website, I plan to continue to post news and interviews like this one here modified for this blog. The website will offer more links, a glossary, some surprise, and a whole lot more.

Stay tune, but I digress.

This clonal heterogeneity discussion is very important stuff on how our cancer evolves and what it means when we consider therapies.


·     Cancer by its nature is genomically 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.
·     Those changes may have significant implications for how to best manage our cancer.


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.


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 indicator 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 critical research with enormous implications for how we should treat our cancer. 

More to come.

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Blogger Dr. La Verne said...

Dear Brian: Please let me know what I can do to help you with your non-profit. We can talk on the phone soon. -- LV

March 16, 2015 at 2:19 PM  
Blogger Shulamit said...

Dear Brian: Your interviews are interesting and informative. You do it well. However, some of your interviewees--Dr. Cathy Wu is a case in point--drop their voices after starting out strong, and their final words are inaudible. Is there any way you could coach them beforehand to remember that they are speaking to an audience and not just to you? It might help. Thanks.

March 16, 2015 at 8:24 PM  
Anonymous Anonymous said...

Thanks for the series of interviews. In my experience doctors rarely share this depth of knowledge with the average patient. On the topic of ibrutinib resistance, it might be worthwhile to discuss mono therapy vs. ibrutinib combined other agents such as rituxan or bundamustine, just to mention two. If the durability of response is better using combinations we should have that information up front. Better decisions might lead to better outcomes.

March 23, 2015 at 6:23 AM  

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