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Dr. Abruzzo

Dr. Lynne Abruzzo is an expert in hematopathology and cytogenetics. Her days at MD Anderson Cancer Center are spent analyzing blood samples from CLL patients. Her work has had an impact on our understanding of the complexities of genetics in CLL. She is currently analyzing blood samples of 11q- patients looking for genes other than the ATM gene which may have significance in the biology of 11q- CLL. Read more about her project here.

The Jaffe's and Dr. Keating
The Jaffes with Dr. Michael Keating
The Partner Perspective section in the April 2011 issue of Tidbits featured a story on Dr. Ed Jaffe. He climbed Mount Kilimanjaro in July 2011 in the name of cancer research. Dr. Jaffe surpassed his fundraising goal and recently presented CLL Global with a contribution of $50,000. MANY THANKS to the Jaffe family for their hard work and dedication! 

Research Momentum 
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Dr. Michael Keating responded to questions asked by Andrew Schorr, founder of Patient Power, in "An Expert's Perspective" session. Listen to the webcast at CLL Global or Patient Power.  



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October 2011 



We always refer to chromosomal abnormalities but don't spend a lot of time drilling down to the details of each abnormality. This month we will begin a series focusing on each of the common chromosomes used as prognostic markers in CLL. Today we focus on chromosome 11. 


Below you will also find a new section called "Clinical Trials and You" along with a follow-up to a "Partner Perspective" story from April. We also just published latest issue of the CLL Global Research Momentum newsletter. Read on! 


Focus on: 11q-


11q-, 13q-, trisomy 12 and 17p- are the most common CLL abnormalities detected by the diagnostic tool florescence in situ hybridization (FISH). Approximately ten to fifteen percent of CLL patients have 11q- either as the sole chromosomal abnormality or as the predominant abnormality. 11q- is associated with a short time to treatment from diagnosis and short periods of remission.


There are at least two contributing factors to the peskiness of 11q-. Patients with an 11q- abnormality often have large lymph nodes, also known as bulky disease. This means that the CLL cells reside primarily in the lymph nodes and are protected by their microenvironment (the environment in which the cells dwell and interact with other cells and molecules). It is much more difficult for drugs to eliminate these cells when they are under microenvironmental protection.


11q chromosome


Image of chromosome 11. The portion highlighted by the yellow arrow is where the ATM gene is located and where abnormalities and deletions occur in CLL.   


Secondly, the ATM gene (ataxia telangiectasia mutated), located in the region affected by 11q- abnormality, is generally deleted or dysfunctional. A properly functioning ATM gene helps to control the rate at which cells grow and divide and is responsible for repairing defects or breaks in DNA. Much more needs to be learned about ATM and other genes in the 11q- region to fully understand its role in 11q- CLL. While genetic research continues, scientists are taking other measures to overcome the 11q- obstacle.


What we know about 11q-: 

  • 11q- is highly sensitive to FCR-like therapies even in older patients.
  • Less intensive therapies prior to FCR-like therapy do not influence response.
  • 11q- patients have a high complete remission (CR) rate but shorter remissions than average (see figures below).
  • Patients who are minimal residual disease (MRD) positive after treatment have shorter remissions than those who are MRD negative.
  • Relapse is currently inevitable.
  • The survival rates are the same as other genetic markers except for 17p-, even though 11q- patients have shorter remissions. 

 11q response rates11q- relapse rates


Short remissions and inevitable relapse may be partly attributed to bulky disease. Consolidation therapy, which is treatment given after initial therapy to maintain control of disease and enhance the remission, may help change the current statistics. New drugs like lenalidomide and BCR inhibitors are being looked at as potential consolidation therapies. (For more information on BCR inhibitors, click here.)


Also, BCR inhibitors force CLL cells from lymph nodes and into the blood stream where they are more susceptible to treatment. The hypothesis is that BCR inhibitors can reduce bulky disease, thereby eliminating MRD and prolonging remissions. A consistent, sustained decrease in lymph node size has been seen, but should not be considered indicative of full clinical trial results. More data and time will provide answers.


While progress has defintely been made in the understanding of 11q-, there is still more work to be done. 


Going forward:

  • A better understanding of the ATM gene and 11q are needed with further investigation of DNA repair capabilities of ATM. The goal is to eventually exploit this defect.
  • BCR inhibitors will continue to be analyzed.
  • Other new agents need to be explored in 11q- patients.

The Patient - A Key Piece to the Puzzle


CLL Global articles generally focus on up-to-date CLL research from across the globe. However, from time to time we like to take the opportunity to acknowledge the single most important aspect of conducting clinical research: the patients who are willing to participate in experimental trials.


As if it is not hard enough to be diagnosed with the "c" word, patients who are introduced to clinical trials usually have arduous disease that will not go away with standard therapies. After agreeing to participate in a clinical trial, patients then donate their time and bodies to an unknown outcome.    

 globe puzzle

While the praise to patients may not be frequently expressed in scientific articles, we all recognize the patients' contribution. Without patients willing to fight for a chance to help themselves and to help others, medical research would not have advanced to where it is today and where it is going tomorrow.


The scientists with visions and the clinicians who carry out the trials also have important roles to play. The bottom line is we are all in this together. We all serve as necessary pieces needed to complete the puzzle that is a cure.


IWCLL, a CLL Global Alliance meeting and ASH will all take place over the next few months. The latest research will be presented and discussed. We will bring you the highlights. Stay tuned.



CLL Global Research Foundation