tidbits header .

Bits and Pieces from the CLL Global Community   




More About Us


Tidbits Archives






Find us on Facebook

 Join our Cause




Find us on Facebook



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


Information about CLL


What we are doing to defeat CLL



Andrew Schorr, founder of Patient Power, has been busy interviewing CLL experts.

New interviews can be found on the CLL Global Player titled "The Future of FCR for CLL with Dr. Michael Keating" and "An Expert's Perspective on Advancing Treatment Progress for Blood Cancers" which features one of CLL Global's Scientific Advisory Board members, Dr. Steve Rosen.

Dr. Jeff Sharman of Willamette Valley Cancer Institute in Eugene, Oregon provides his insight on new CLL treatments.
An Expert's Perspective: Why New CLL Treatments Supersede FCR


CLL Global is thankful to have been the recipient of a recent fundraiser from one of our supporters, Carol Preston, who raised over $5,500! More information to come in the next


Email us if you have any questions. We are available to help plan and craft your fundraiser.  




You may have to scroll through each newsletter to find the article.

Articles are listed from most recent to oldest.

Antibodies and IVIg


Make a donation to CLL Global in honor of your loved one this Valentine's Day. It is a unique, special way to show your loved one you care. Email us today and we will create a Valentine's Day themed card.



CLL Global exclusively funds CLL research. 

The president and CEO of CLL Global, Dr. Michael Keating, has been involved in CLL research for a few decades. He knows the who, what and when of CLL research and guides the organization accordingly.  

Only 5% of total funds are used for administrative overhead. This means that 95 cents of every dollar donated goes straight to CLL research.   
CLL Global operates on a dollars in, dollars out basis. CLL Global prefers to utilize its resources as efficiently as possible.


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.




donate button  



February 2013



Once a year, members of the CLL Global Alliance travel to Houston to discuss updates in CLL research. Participants leave with new ideas and plans for action. This year's meeting was no exception.


Reversing the defects of a CLL patient's immune system was merely once an idea. Now it is a reality because of the commitment and persistence of researchers. It is the topic of our last article in the immune system series.


Keep reading to find out more.


Houston Alliance Meeting   


Alliance LogoCLL Global Alliance members gathered in Houston on January 26 and 27, 2013 for the semi-annual Alliance meeting. The Alliance is a collaborative group of CLL investigators from the United States and Europe. Members have been actively participating since 2008, and during this time a true sense of camaraderie and trust has developed which accelerates new collaborations and ideas for research approaches.


While all research meetings involve scientific presentations, Alliance meetings benefit from the dialog generated during and after the presentations rather than the presentations themselves.  


Alliance members participate in a multitude of scientific meetings throughout the year and are in tune with the latest research endeavors. Rather than having presentations full of large amounts of data, experts from each field of research were encouraged to provide new information from an opinion stand-point.


The main topics of discussion for this particular meeting included immune-based therapy, genetics and the increasingly complex interactions between CLL cells and other cells in the body. This was then followed by extended discussion from the group. The point of this meeting was to be exploratory with less data presented and more imagination and discussion.  


Genes provide the make-up of every cell, so genetic research is an important field for finding answers. Next generation sequencing techniques, which analyze every single gene in the DNA of CLL cells, provide an opportunity to focus attention on the consequences of genetic abnormalities.


Through next generation sequencing, genes called NOTCH, SF3B1 and MYD88 have been discovered to play a role in CLL. Early data on their correlations to treatment responses were discussed as well as how to address these genetic abnormalities in terms of treatment. Some researchers will continue to look at how genetic abnormalities affect patients' outcomes to available therapies. Others will develop therapies which specifically target genetic abnormalities.


A group of Alliance members discussing research approaches during a break.

Current treatments are always discussed with an opportunity to point to progress made in the last six months. Versions of chimeric antigen receptors (CARs) are already being used in clinical trials. It is too early to determine the role CARs will play and whether genetic factors affect the success of this treatment. The same is true for the kinase inhibitors like ibrutinib. Responses have been very impressive, but time will tell if certain genetic abnormalities affect the duration of response.


The CLL microenvironment (the environment in which the CLL cells reside in the body that include a matrix of other cells and molecules that provide support to CLL cells), may also throw some curve balls into the equation. Researchers now have a much better grasp on interactions that take place between CLL cells and other cells, but until a patient is treated with a new drug no one knows for sure what will happen.


Solutions to such complicated topics cannot be established over a two day period, but researchers left Houston with exciting new ideas to explore. The CLL landscape is changing and has been for a while, making it an opportune time for researchers to think outside of the confines of standard approaches. The take home message was that this is a truly exciting time for CLL research and a pivotal opportunity to close in on curative strategies for CLL.



Immune System: Immune-Modulators 


We have spent the last several issues of Tidbits discussing the relationship between CLL and the immune system. (Links to previous articles can be found in the side bar to the left.) Researchers have spent many years studying the biology of CLL cells (malignant B-cells) and their relationship with the immune system. Several methods are under investigation to reverse the ways that CLL cells negatively affect the immune system. We will explore some of the mechanisms being targeted and drugs being tested.

Immune cells (blue) attacking cancer cell (yellow). Imaged obtained from oncosec.com


CLL Cell Mobilization from Sanctuary Sites: CLL cells hang out in the lymph nodes for protection and nourishment. When CLL cells are forced into the blood stream, they are more susceptible to death. Ibrutinib and idelalisib (formerly known as GS-1101 and CAL-101) are becoming well-known for their dramatic results in reducing lymph node sizes and eliminating CLL cells. These and other similar drugs block adhesion proteins which enable the CLL cells to stay in the lymph nodes, and thus push the CLL cells into the bloodstream.  


Enhanced T-cell Co-Stimulation:A major component of immune dysfunction in CLL is defective T-cells, which are important immune cells. In a healthy individual, T-cells and B-cells work together to keep the body free from foreign invaders. B-cells and T-cells stimulate, or activate, each other through shared signals. Studies have demonstrated that CLL cells prevent T-cells from properly functioning, but this relationship is not fully understood.


Lenalidomide is a relatively newer treatment offered for CLL patients. It is considered an immune modulator, meaning that it enhances the capabilities of the immune system. It offers several benefits for CLL patients, including reversing the defects of T-cells. Researchers do not fully understand how lenalidomide does this in CLL patients. It is not yet FDA approved for CLL and is not appropriate for all patients.


The B-cell and T-cell relationship is an appealing way to target CLL cells. Teaching T-cells to attack malignant cells is something researchers have been studying for years. Chimeric antigen receptors (CARs) may be a solution. CARs are receptors that are genetically inserted into T-cells and then expressed on their surface. CARs enable T-cells to seek out a specific molecule and stimulate the T-cells to attack and kill the cell expressing the target molecule found on CLL cells.


Repair of CLL B-cell Antigen Presenting Function: B-cells are producers of antibodies. Before a B-cell is capable of producing antibodies, it first functions as an antigen presenting cell. This means that the B-cell encounters an antigen, or foreign invader, and takes the antigen to "present" to a T-cell which in turn helps the B-cell multiply and produce antibodies against the specific type of antigen (see image below). CLL cells are poor antigen presenters, and there are few healthy B-cells in a CLL patient, so there are lower levels of antibodies being produced.  


In addition to what was mentioned above, lenalidomide can also repair the antigen presentation function in CLL cells. Once again, the exact mechanisms of lenalidomide in CLL are not well understood. But, researchers do know that it enhances immunity against CLL cells and at the same time reduces the survival mechanisms used by the CLL cells.

Imaged obtained from www.niaid.nih.gov.

Gene therapy is another mode of repairing the antigen presenting function in CLL cells and also serves as a targeted therapy. Gene therapy is a process where a gene is inserted into a cell to change how the cell operates. A gene can be inserted into a CLL cell so that the cell develops an antigen on its surface and subsequently presents this antigen to a T-cell. The T-cell then destroys the CLL cell. Basically, the gene makes the CLL cell mark itself as a target for destruction. Phase I clinical trials using gene therapy for CLL were successfully conducted a few years ago, but further action has yet to be taken.


T-cell therapy:T-cell therapy also capitalizes on the relationship between B-cells and T-cells. Allogeneic stem cell transplantation, where a donor supplies stem cells to a patient, is currently the only FDA approved therapy that utilizes T-cells to target CLL cells. A transplant basically replaces the patient's immune system with a healthy immune system which should recognize the cancer and kill the cancer cells. There can be significant side effects and toxicity associated with a stem cell transplant, although management of the side effects is improving.


T-cells are primarily responsible for eradicating cancer cells as part of a transplant. This knowledge prompted the development of CARs (mentioned above). By eliminating the other cell types infused in a stem cell transplant, and teaching the T-cells to only target specific molecules, there should be a significant reduction in risk. CARs are being tested in early stage clinical trials.     


Information for this article retrieved from: Riches, J.C., et al. Immune Reconstitution in Chronic Lymphocytic Leukemia. Current Hematologic Malignancy Reports. 2012;7(1):13-20.  


There are those who act and those who accept. We chose to act so that CLL patients and beyond can benefit from our actions. You can chose to act for the same reason.

Until next time, be happy and well.



CLL Global Research Foundation