tidbits header CLL Global logo .

Bits and Pieces from the CLL Global Community   




More About Us


Tidbits Archives


If you have recently been diagnosed with CLL, you probably have questions. 


Information about CLL


What we are doing to defeat CLL






Find us on Facebook

 Join our Cause




Find us on Facebook


Research Momentum
The latest issue of the CLL Research Momentum was recently mailed out.

Email us your mailing address if you currently do not receive hard copies and would like to be added to the mailing list.



Now that Halloween has passed, the Holidays are here. Whether this statement makes you cringe or clap your hands in joy, you cannot deny the amazing deals on Cyber Monday.


Shop at your favorite stores online through  GoodShop, designate CLL Global as your organization and a percentage of your purchase will be donated to CLL Global. Stores like Amazon.com, Macy's and Brookstone also offer coupons and deals exclusive to GoodShop.




Do you have questions about the immune system or CLL?
Email us and we will provide answers to your questions as the series continues.

This video explains apoptosis (programmed cell death) and how cancer develops.

Understanding Your Blood Tests: Immunoglobulin, Complete Blood Counts, Platelets and More
Understanding Your Blood Tests: Immunoglobulin, Complete Blood Counts, Platelets and More

The Board of Directors for CLL Global recently gathered in Houston for their biannual meeting.

One thing is clear: Your donations have been well managed. This keeps CLL Global in an optimal position to fund outstanding CLL research wherever it is needed and to be a reliable resource for the CLL research community.
The board approved proposals to amp up funding for CARs (link loads slowly) and bio- statistics in addition to funding individual and Alliance grants that are part of the regular budget. The board will meet again in the Spring of 2013.
to meet the CLL Global Board of Directors.  


Is there something specific you want to read and learn about? 


Let us know if you have any comments or suggestions for improvement.


You are the reason CLL Global exists, and we want to hear from you.






  We have been feeling especially proud of our accomplishments lately. Research is bustling and some of our large endeavors are coming to fruition.   


As we carry our heads high, you should too. Because we would not be here without you.  CLL Global victories are all of our victories.


So thanks for everything.  



Instead of receiving another fruit basket this year, tell your friends and family that a gift to CLL Global Research Foundation would have a positive impact on your life.


They can visit our donate page or contact us via email. 


donate button  



November 2012



The theme of this month's issue of Tidbits is transition. The project update this month talks about the transition in how CLL cells are studied.

The immune system series continues below. However this month's article transitions from general information about the immune system to the development of CLL. Why? Because CLL is a disease of B-cells, an important cell in the immune system.

Hematologic Malignancies 2012 was recently held in Houston. The presenters made it clear that the management of CLL patients is transitioning. Read the details below.  

Project Update: Overcoming CLL Drug Resistance

Drug resistance has been a major challenge in the clinical treatment of CLL patients. In the past, researchers were perplexed that a drug would work well in the laboratory but was not as effective when given to patients. It is now known that the microenvironment (the tissue environment where the CLL cells reside in the body, i.e. lymph nodes, bone marrow and spleen) provides protection and resistance to drugs.


Previously, CLL cells were isolated from patient blood samples for laboratory testing. Testing isolated CLL cells did not subject the cells to the factors in the microenvironment. This meant that the cells in the lab were not responding to drugs in the same way as cells in the body. Now CLL cells are co-cultured with stromal cells to mimic the microenvironment. Stromal cells communicate with and support CLL cells.

Dr. Peng Huang 


For his Alliance project, Dr. Peng Huang (MD Anderson Cancer Center) has been conducting laboratory studies to better understand the interactions between the CLL and stromal cells. Dr. Huang has discovered an important pathway by which stromal cells help the CLL cells survive and resist the cytotoxic effects of drugs. He has also developed strategies which overcome the drug resistance caused by stromal protection.


As a cell produces energy through a process called oxidative metabolism, it releases molecules such as ROS that can be harmful to the cell. Glutathione is a major cellular antioxidant responsible for removing ROS, detoxifying other harmful molecules, and promoting drug resistance.


CLL cells have limited ability to produce glutathione due to low expression of a critical molecule. However, stromal cells feed CLL cells with a chemical needed to make glutathione. This helps CLL cells to survive under ROS stress and resist drug treatment.


Lab studies indicate that abolishing glutathione protection leads to the enhancement of a drug's toxic effect on CLL cells. Dr. Huang has tested two compounds, PEITC and SSZ. Both are successful in removing the drug resistant shield provided to CLL cells by the stromal cells.


PEITC (phenethyl isothiocyanate) is a molecule found in cruciferous vegetables like broccoli and Brussels sprouts. It reduces glutathione in CLL cells and prevents removal of the drug molecules from the cell. SSZ (sulfasalazine) is currently used for rheumatoid arthritis and inflammatory bowel disease. It was recently found that SSZ can block stromal cells from providing the chemical needed for CLL cells to produce glutathione. 


Cruciferous vegetables like cabbage, broccoli and cauliflower have shown anticancer activity against many cancers. Image provided by lancastria.net 

Dr. Huang also tested combinations of PEITC with standard chemotherapeutic agents. There was a notable increase in the effectiveness of the chemotherapy, even in the presence of stromal cells. As an added benefit, PEITC is effective in killing CLL cells with chromosome 17p deletion. This is important because cells with 17p deletion are often resistant to conventional therapeutic agents.


A clinical protocol has been developed to test PEITC in humans. The next step is to submit the protocol for FDA approval. While Dr. Huang has been studying PEITC for several years, the work done through his Alliance project has helped him to provide needed data and documentation for planning future clinical trials. SSZ has not been as extensively studied in CLL, but initial results are promising and the compound will be further investigated. 



Immune System 101: The Development of CLL


The last three issues of Tidbits laid out the basics of the immune system. If you need a refresher, the links to previous issues are in the side bar to the left. Now that we understand the components of the immune system and how it works, we can move on to the development of CLL which is a disease of the immune system.


CLL stands for chronic lymphocytic leukemia: leukemia is cancer which affects blood cells; lymphocytic specifies the type of blood cells, lymphocytes, which are affected; chronic refers to the often slow rate of development of the disease. The majority of cases affect B-cells, a type of lymphocyte, which play an important role in the immune system by producing antibodies that target antigens. A very small percent of CLL cases affect T-cells, another type of lymphocyte. T-cell CLL is a rare disease and is often called T-PLL (prolymphocytic leukemia). CLL Global refers to CLL in the context of B-cell CLL unless otherwise specified.

CLL in the peripheral blood as seen under a microscope. The pink cells are red blood cells. The purple cells are white blood cells (lymphocytes). Experts can often determine which lymphocytes are CLL cells by sight, but conduct other tests to verify. Image provided by ASH image bank: imagebank.hematology.org 


Almost all cells in the body grow and reproduce. When cells become damaged or old, they die (a process called apoptosis). Signals within the cell and the body control this cycle. When this cycle is disturbed, cancer can form. Many types of cancer develop because the cells reproduce without being detected by the immune system. In addition, CLL cells suppress other immune cells, thereby impairing immune defenses. These rogue CLL cells accumulate in the lymph nodes, bone marrow and spleen and crowd out healthy immune cells.


There is evidence that both genetic and environmental factors can cause alterations in the DNA, leading to the development of CLL. For example, the incidence of CLL is much higher in the Ashkenazi Jewish population compared to the Sephardic Jewish population. Researchers are analyzing and comparing the DNA of both Ashkenazi and Sephardic Jews to find a genetic link. Also, the Department of Veterans Affairs has identified exposure to Agent Orange as a potential cause of CLL.


Many patients find out they have CLL through routine blood work. Others experience symptoms like fatigue, night sweats and/or swollen lymph nodes which will prompt a physician to run blood tests. The most common first diagnostic indicator of CLL is a high absolute lymphocyte count, usually around 5,000 or greater. More specific tests should be conducted to confirm the diagnosis, as other diseases can also increase the lymphocyte count.


Hematopathologists are scientists trained to diagnose blood diseases. They look at proteins expressed on the surface of the cells which indicate the type of disease. All cells have CD proteins on their surface which number from CD1 to CD350. CLL is diagnosed when there is expression of proteins CD5, CD19, CD20, and CD23.   


Typical markers found on CLL cells. Image provided by www.campath.com.

The CD proteins primarily act as receptors but can serve other functions. Interestingly, CD5 is a protein normally found on T-cells, but for some reason is activated on CLL cells. It is currently not known why this happens or the significance, but new research is showing that the role of CD5 may be quite important in CLL.


We have covered some of the how and what of CLL. There is much more to discuss, and discuss we will. Next month we will talk about more characteristics of CLL and introduce antibodies which are a key component of B-cell function and the immune system.



Hematologic Malignancies 2012   


Big changes are happening in the management of CLL, not only with new treatment options, but also in how doctors view the disease to make these treatment decisions. This was the take home message from experts who presented at the Hematologic Malignancies (HM) 2012 meeting held in Houston in October. At the HM meeting, scientists who specialize in hematologic malignancies (blood cancers) such as leukemias, lymphomas and myeloma educated their peers on the latest research updates.


The list of CLL presenters at HM 2012 included some of the top names from around the world. Dr. Kanti Rai (the physician after which Rai staging was named) provided perspective on the transition in CLL management, noting that the list of prognostic indicators continues to grow and to provide better insight into the disease. Dr. Rai emphasized that the disease course varies from patient to patient regardless of their Rai or Binet stage at initial assessment. He stated, "Clinical staging is

Dr. Kanti Rai presenting at HM 2012.

fine, but it is not enough and we have to move forward."


Other CLL presentations supported Dr. Rai's comments. CLL is notorious for having the "watch and wait" treatment approach where therapy is held until it is warranted based on symptoms and staging. Previously, doctors did not have solid evidence that early treatment is beneficial for patients. However, this mindset is changing. Newly discovered genetic mutations and correlating data is certain to lead to some patients being treated earlier than they would have previously.


During his morning presentation, Dr. Michael Keating implied that patients who have genetic mutations implicating eventual disease progression may benefit from earlier treatment. For example, Notch1 is a recently discovered gene that is expressed in 25 to 50 percent of patients with the trisomy 12 FISH abnormality. It is thought to be linked to more aggressive disease. These patients, and others with genetic abnormalities indicating a need for therapeutic intervention, may benefit from earlier treatment or a different type of treatment than those with less aggressive disease.


Expanding and refining subgroups of patients is one example of the future of CLL management. Other items on the CLL agenda at HM 2012 were the new targeted treatments, genetics, transplantation, microenvironmental support (cells in the body which nurture CLL cells) and treatment improvements for elderly patients. All CLL presentations at HM 2012 emphasized the transition from trying to treat CLL as one disease to understanding its complexities and working to benefit all spectrums of the CLL patient population.  


"Not what we say about our blessings, but how we use them, is the true measure of our thanksgiving." - W.T. Purkiser

This summarizes how we feel about your support. We hope you agree. Until we meet again, be happy and well.  


CLL Global Research Foundation