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Issue #14November 2011
In This Issue
Check Your Mailbox
DBAR Update
DBA Support Group
Show Us Your Logo!
DBA Fact
Happy Thanksgiving
DBAF Journal Club

Coming Soon...
Check Your Mailbox!


mailbox

The Diamond Blackfan Anemia Foundation is committed to supporting DBA patients, families, and research.  It is only through the support of our friends and families that we can continue to fulfill our mission. We need your help!

  

As DBA families, each one of us shares the challenges of living with a rare disorder, as well as the hope for better treatment options and ultimately, a cure. By working together, the DBAF hopes to continue funding critical research, supporting scientific conferences, sponsoring Camp Sunshine, and providing our families with information.

Your partnership with us is essential to the DBAF's success and growth.  Your support allows us to fund   independently reviewed and approved research projects from around the world and provide information and support to our patients and families. We rely on you for your important financial support and your involvement.

 

In the next few weeks, you will be receiving information on how YOU can make a difference. Watch your mail box for this important information. We are hopping for YOUR participation.

 

    

The Diamond Blackfan Anemia Foundation sincerely thanks our families and friends for their generosity, hard work and continued efforts. It is because of their commitment that we are able to fulfill our mission for patients... for families... for research.

To ensure that you are receiving all the current information, please be certain that your contact information is up to date.  Visit our secure website and register today! http://www.dbafoundation.org/registration.php  

 

 THANK YOU!    

 

Upcoming Events

 

 

DBA Support Group   

November 30, 2011
7:00 - 8:30pm   

New Hyde Park, NY 

Contact:  
Ellen Muir
emuir@nshs.edu
1.877.DBA.NURSe

 

   

 

Ongoing Fundraisers 

 

Mixed Bags Designs
Contact:

Vickie Lamb
Use Code: 69293  

To order online visit:

 

http://www.mixedbagdesigns.com/

 

 

 

Wristbands Available

Contact:
Twila Edwards

twilak@cox.net 




Tribute Cards Available

(2 styles)

In honor of...

In memory of...

Contact:

Dawn Baumgardner

dbaumgardner@dbafoundation.org

716.674.2818



donation donation



DBA Cookbooks Available

Contact:

Betty Lightner

betty.lightner@gmail.com

 

To download your order form:
http://issuu.com/bhivemom/docs/cookbook_order_form-pdf


cookbook cover 




Good Search/Good Shop

Raise money for DBAF just by searching the web and shopping online!

Just download the GoodSearch - Diamond Blackfan Anemia Foundation - DBAF toolbar at http://www.goodsearch.com/toolbar/diamond-blackfan-anemia-foundation-dbaf

   

Search the Web now Money-saving coupons


 

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Quick Links

Join the DBA Yahoo Group

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:: 716-674-2818
The Diamond Blackfan Anemia Foundation (DBAF) is committed to keeping you updated and connected to the entire DBA community. The Diamond Blackfan Anemia Foundation is YOUR Foundation!  We encourage you to share your ideas, photos, and stories for our website and upcoming newsletters. Contact us at DBAFoundation@juno.com.

The Diamond Blackfan Anemia Registry Update   

by Eva Atsidaftos, MA, CCRP

DBAR Research Coordinator

 

Greetings from the Diamond Blackfan Anemia Registry (DBAR)! For those

Eva
Eva Atsidaftos 

who are not familiar with who we are, the DBAR is a research organization dedicated to studying Diamond Blackfan anemia in order to improve our understanding of this very rare disorder, to educate families and physicians, and to ultimately improve treatment options. We accomplish this by collecting and analyzing medical information on DBA patients. This research could not have been possible if it weren't for all the patients that are registered in the DBAR, so thank you to all those that have enrolled.  

 
This has been a very exciting year for the DBAR. We have seen much progress in improving our understanding of this very rare disorder, DBA.

 

 

Some highlights of the DBAR Research Accomplishments for 2010-2011

  • Enrolled 14 new subjects in the DBAR (a 2.3% increase from last year)
  • Updated the demographic, treatment response, and clinical information for 621 existing patientsenrolled in the DBAR
  • Continued to serve as a resource for information to patients, families, physicians, collaborators, and health care professionals
  • Continued the collection and storage of DNA and cell lines from DBA patients and their families in the DBA Biorepository; currently we have acquired 156 blood samples from DBA affected patients and 240 family members. These samples serve as a resource for collaborative studies that will help identify the gene abnormalities that cause DBA.
  • Analyzed the risk of cancer for DBA patients in collaboration with the National Cancer Institute:
    • Cancer and myelodysplasia were identified in 22 patients with DBA. One patient had 2 malignancies and myelodysplasia for a total of 24 events.
    • Results were presented at the annual meeting of the American Society of Pediatric Hematology/Oncology in April 2011.
    • The manuscript has been submitted for publication.
  • Facilitated the discovery of one more DBA gene (RPL26) and six potential candidate genes of unknown significance, that also encode for ribosomal proteins, in collaboration with Children's Hospital Boston. The DBAR assisted by procuring samples for the Gene Discovery project. An oral presentation was made at the annual meeting of the American Society of Hematology in December 2010. Again the manuscript has been submitted for publication.
  • Continued gene discovery efforts for patients are ongoing to aid in diagnosis and potentially assist in treatment options in the future
    • In 2008 a DNA Resequencing & Genotyping Program grant was awarded to the DBAR through the National Heart, Lung, and Blood Institute to resequence all 80 ribosomal protein genes; the results were analyzed in 2010.
    • In collaboration with the National Human Genome Research Institute and Johns Hopkins University, we analyzed a group of patients who did not have any mutations found from the resequencing project. This time a different method was used that looks for deletions (missing genes).
    • Multiple DBA patients were found to have deletions of previously known DBA genes, thus confirming their diagnosis. A poster presentation was made at the annual meeting of the American Society of Hematology in December 2010 and the manuscript will be published in the journal Blood in Dec 2011.
    • From the resequencing project, one transfusion dependent patient was found to not have DBA, but instead have another disorder, 5q- myelodysplastic syndrome (MDS). The patient was placed on lenalidomide; a drug that is known to be effective in 5q-MDS, and the patient went into remission (not requiring any transfusions). This finding was reported as an oral "late-breaking" presentation at the annual meeting of the American Society of Hematology in December 2010.
    • A protocol to perform whole exome sequencing (WES) (which looks at all the genes and for associations to DBA) on patients without identified mutations or deletions has been written in collaboration with the National Human Genome Research Institute, and has received funding from the Diamond Blackfan Anemia Foundation; final institutional review board approval pending.
  • Invited to write "How I Treat DBA" for the journal Blood; published in November 2010 and distributed to physicians, other health care professionals and families as a source document
  • Embarked on three clinical treatment research protocols for transfusion-dependent DBA patients; two of which will open by December 2011
            o  The amino acid Leucine is to be offered to transfusion- dependent  patients over age 2 years
            o  A new "bone-building" drug which was found to have a side  effect of increasing the patients' hemoglobin (a desirable effect for DBA patients) will be open to adult transfusion-dependent DBA patients to see if indeed it will decrease their transfusion requirement.
  • Numerous manuscripts and abstracts have been published during the past funding period through collaborative studies with the DBA Registry:              

The DBAR would like to take this opportunity to thank the DBA Foundation and DBA Canada, for awarding us with funding to further support our endeavors. We would also like to thank all the families who have worked so hard to make all this funding possible.

 

We would also like to take this opportunity to invite all patients to join us in these research efforts. Being that DBA is such a rare condition, it is imperative that every DBA patient enroll in the DBAR.

 

Please feel free to call or email me to request Registry enrollment forms or to check on the status of your enrollment.

Contact:

Eva Atsidaftos/ DBAR Research Coordinator

Email: eatsidaf@nshs.edu

Toll free: 888-884-DBAR (3227)

  

DBA Support Group - New York 

support group flyer
 



Take the Challenge ~ Show Us Your Logo 

Gately raffle table
 T-shirts, hats, coffee mugs, face paintings,  tattoos, bags,  pumpkins ... our logo is showing up everywhere! We are thrilled that our beautiful logo is proudly being worn and displayed by patients, families, and friends.

 Kevin Gately's life and legacy live on in the hearts of those who knew and loved him and in the hearts of his DBA family.  Kevin's family continues to honor his memory through their dedication to the Kevin J Gately Foundation. Kevin's tragic death on July 26, 2010, just five days after his 29th birthday,  from complications of iron overload motivated their efforts to keep Kevin's memory alive. This year's golf outing held on October 17 was yet another testament to the commitment the Thompson and Gately families have to Diamond Blackfan Anemia and our families.  The event raised $6,500 for the DBAF and a $2,000 family sponsorship for a DBA family to attend Camp Sunshine. We are humbled and honored to accept this heartfelt donation.  
 
Here's the challenge:  we'd like to see how many places we canDBAF  Logo show off our logo!  Snap a picture sporting our logo and send us your story. Draw it, print it out, wear it, wave it, tattoo it, carve it... be creative! Take us to school, on vacation, to the hospital, on a plane, to the game, in your home... anywhere!  Show us your logo!  Send your photos and stories to DBAFoundation@juno.com. 


DBA Fact #7    

Ellen Muir

Our Facebook page posts DBA facts written by DBA nurse, Ellen Muir, RN, MSN, CPON. We are pleased to share these fast facts with our patients and families. Thanks, Ellen! 

 

The Bone Marrow Examination- What is it and Why should it be done?

 

The bone marrow is the "factory" where hematopoiesis takes place (that is a fancy word for the production of the cells in the blood - red blood cells, white blood cells and platelets). A bone marrow examination is a test that looks at the cells in the bone marrow, to see how many there are and what they look like. The bone marrow is found in the center of the bones and is made up of both spongy bone and liquid marrow.

 

Most of the time, the information from the bone marrow exam can be useful in diagnosing DBA and rule out other disorders which may cause a change in the marrow (such as leukemia, aplastic anemia or myelodysplastic syndrome [MDS]). A bone marrow examination is usually done to make the initial diagnosis of DBA. If this hasn't been done, it is recommended to be done before starting steroids as the medicine can change the appearance of the cells. Aplastic anemia, acute leukemia and MDS have been reported in DBA. For this reason, we perform a bone marrow evaluation if there is a change in blood counts seen on the complete blood counts (CBC), such as a steady decrease in white blood cell count or platelet count. We do not perform routine yearly bone marrow exams in patients whose blood counts are stable and have not changed.

 

A Bone Marrow Aspirate is usually done from the posterior (back) hip (iliac) bone. Rarely it can be done from the anterior (front) hip bone or the chest bone (sternum). The area to be used is numbed with a topical anesthetic, usually lidocaine. The area is then sterilely cleaned and a needle is placed into the bone. Liquid marrow is removed with a syringe and sent for the following tests:

Morphology of the bone marrow is usually done by the hematologist or the pathologist or both. This is where the bone marrow is spread on a slide and stained with special stains that will "color" the blood cells, making them easier to identify under the microscope. The cells are counted and viewed for their appearance. Abnormalities in the number of cells can give information about potential Aplastic anemia (too few cells of all three cell lines) and abnormalities in their shapes or sizes can be important to diagnose myelodysplastic syndrome or leukemia.  Cytogenetics is the study of the structure of DNA within the cell nucleus. This is done in two parts:

Karyotype gives information about the number of chromosomes. A normal person has 23 pairs of chromosomes; one of those pairs is XX (female) or XY (male). An extra chromosome (trisomy) or a missing chromosome (monosomy) will indicate a disease process (for example, an extra chromosome 21 is associated with Down Syndrome). Fluorescence in situ hybridization (FISH) provides researchers with a way to see and map the genetic material in an individual's cells, including specific chromosomes or portions of chromosomes.

 

A Bone Marrow Biopsy can be done at the same time as the bone marrow aspirate. A piece of the spongy bone is removed, usually using the same needle and puncture area. The biopsy specimen is removed and sent to pathology for:

Cellularity - This is the percentage of cells in the specimen. Bone marrow contains hematopoietic stem cells and fat cells. If a sample is hypocellular, it has fewer than the expected number of hematopoietic cells (cells that mature into red blood cells, white blood cells and platelets). If a sample is hypercellular, it has more than the expected number of hematopoietic cells. Cellularity is age dependent -in newborns, all marrow is hematopoietic (shows 100% cellularity). With age, hematopoiesis (the number of cells) decreases, and the amount of fat increases. Normal cellularity of an adult bone marrow ranges between 30-70% and changes under pathological conditions- a marrow is reported as hypercellular (over 70%), normocellular (30-70%) or hypocellular (under 30%).

 

If you have any questions, please don't hesitate to contact me or speak to your doctor.

Ellen Muir, RN, MSN, CNS "DBA Nurse"                          

1-877-DBA-NURSe/ 1-877-322-6877
Happy Thanksgiving!  

Thanksgiving    As we give thanks for all the blessings in our lives, the Diamond Blackfan Anemia Foundation is mindful and grateful to the many families and friends that support our mission with their generous donations and fundraising efforts. Our accomplishments are because of your commitment. Thank you! 

 

Wishing everyone a very Happy Thanksgiving!

 Journal Club 
 

It takes a village. 

What? Hillary Rodham Clinton not your cup of tea? Perhaps you feel her book was a socialist manifesto aimed at destroying the American family, or, perhaps you question whether she wrote the book atall (http://en.wikipedia.org/wiki/It_Takes_a_Village). Yes, the previous reference w
Steve Ellis
Steven R. Ellis, PhD
Research Director
as to Wikipedia... I have no shame.

 

These controversies however, are neither here nor there as far as this month's Journal Club is concerned. Instead, what I hope you can appreciate is that sometimes groups of individuals with diverse skills, when joining together to work as one, can accomplish more than each member of the group working independently.

 

Such a group, led by Jason Farrar and David Bodine, recently published a manuscript in Blood entitled, "Ribosomal protein deletions in Diamond Blackfan anemia." This interdisciplinary group consisted of physicians, genome scientists, and a ribosomologist. Their goal was to identify genes affected in DBA patients whose genes had not been identified by traditional DNA sequencing methodologies. The approach they employed was to scan the entire genome of these patients for lost genetic information focusing on ribosomal protein genes that may have been deleted.

 

Before discussing the results of this study, let me first briefly review gene discovery in DBA. As most of you are aware, the first DBA gene was identified by a group led by Niklas Dahl in Sweden. This group identified a DBA patient that had a chromosome translocation where chromosomes are broken and fused to one another in an abnormal fashion1. The genes present at these translocation breakpoints are typically thought to play a role in the diseases where such translocations occur, which was indeed the case for DBA. In looking at the RPS19 genes in other DBA patients, it was found that several others had mutations predicted to inactivate the Rps19 protein. Thus, we had our first DBA gene, which is now known to be mutated in approximately 20-25% of DBA patients2. Through the efforts of Dr. Hanna Gazda in Boston and the DBA Registry in New York, a second DBA gene, RPS24, was identified, and it too encoded a ribosomal protein3.  A total of 9 DBA genes have now been identified, all of which encode ribosomal proteins. Together these nine genes account for the genes affected in a little over 50% of DBA patients. These genes were largely identified by DNA sequencing and the identification of potential disease causing mutations. Despite these successes, several large scale DNA sequencing efforts have been carried out in DBA patients and still there are many patients whose genes have yet to be identified.

 

One explanation for the failure to identify genes affected in the remaining patients is that, perhaps for these patients, the mutations are in one of the tens of thousands of other genes in the human genome that do not encode ribosomal proteins. This is a formal possibility and one that will likely be explored in a subsequent Journal Club. The other possibility is that, in some of these patients, the ribosomal protein gene affected may be completely deleted. Since DNA sequencing requires that a gene be present for it to be sequenced, sequencing a patient's DNA where one of two ribosomal protein genes is completely missing would just give you the sequence of the remaining normal gene, which would appear....well, normal, and so be missed.

 

So, to address this possibility Farrar et al used SNP-Array genotyping and comparative genome hybridization (CGH) to look for regions of patients' genomes where genetic information was lost. These are amazing technologies where the entire genome can be scanned with enough sensitivity to pick up a change from two copies of a gene to one, and so it is ideally suited for looking for ribosomal protein deletions in DBA patients. Of the 51 patients analyzed in this fashion, 9 were shown to have deletions in known DBA genes including RPS19, RPS17, RPS26 and RPL35A. These results close in on the ultimate goal of identifying each of the genes affected in all DBA patients.  

 

Although no new genes were identified in this study, there were some unexpected outcomes that have important implications. The first is that some of the patients harboring these deletions exhibited what is known as mosaicism, suggesting that not every cell analyzed harbors the deletion. Interestingly, there was a correlation between mosiacism and spontaneous remission. One could envision in patients exhibiting such mosaicism mixtures of apparently normal and mutant cells whose relative proportions exhibit a dynamic behavior, the balance of which may determine disease or remission. These studies provide the first molecular insight into this very important phenomenon. The other unanticipated finding related to RPS17, a previously characterized DBA gene. In carefully analyzing the genome data, it was determined that there were four rather than two copies of the RPS17 genes in the human genome. This observation had not been made before and raised the question as to whether or not RPS17 could really be classified as a DBA gene. This issue comes up since previous reports on RPS17 inferred that a mutation would reduce the amount of functional protein by 50%. But with 4 copies present a mutation in one copy may not be enough to disrupt function and trigger disease. Some of this same ambiguity regarding the number of deleted genes was also evident in the deletion analysis. This ambiguity was resolved by the demonstration that those patients harboring the deletions did in fact have defects in ribosome synthesis indicating a functional consequence of the gene deletion. Consequently, despite the realization that there are 4 copies of RPS17 in the human genome, we can say with restored confidence that RPS17 is a DBA gene.

 

So what of the remaining patients whose genes remain to be identified? I certainly think it is possible that more genes may be identified by sifting through the tremendous amount of data that comes from a whole genome analyses such as reported here. It is also possible that smaller deletions may have been overlooked and still more sensitive technologies may be needed. Or it may be necessary to expand our reach beyond the ribosomal protein genes, searching for the proverbial needle (mutation) in a haystack (tens of thousands of genes) by examining whole genomes at the DNA sequence level. Is this feasible? Yes, with technological advancements in genome science coming at a breakneck pace, approaches unheard of just a few years ago are now within reach. So let us end by coming around full circle. As these technologies advance and require specialized centers and highly trained individuals, progress will more than ever require diverse groups of individuals working together toward a common goal.                 

1.  Draptchinskaia N, Gustavsson P, Andersson B, et al. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999;21:169-175.

2.   Boria I, Garelli E, Gazda HT, et al. The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update. Hum Mutat;31:1269-1279.

3.   Gazda HT, Grabowska A, Merida-Long LB, et al. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006;79:1110-1118.