Issue #8  May 2011
In This Issue
It's Easy to Help
Out of This World
Show Us Your Logo!
Happy Mom's Day
Where Are You Now?
DBAF Journal Club

It's Easy to Help

United Way Logo

Most of us are familiar with the wonderful work the United Way does in our communities. One thing you may not be aware of is that the United Way is broken down into local, individual United Way chapters. Many of these local chapters give 501(c)(3) organizations like the Diamond Blackfan Anemia Foundation, the opportunity to apply to their Directed Donor Program (if offered). This program would allow for company payroll deduction donations to be directed to the DBAF minus a nominal administrative fee.


The Directed Donor Program provides our DBA families an easy way to enable friends, relatives, and co-workers to donate to the DBAF through their company's payroll deduction giving programs. To date, the DBAF participates in over 15 Directed Donor Programs around the country.  We are hoping to add more chapters to our growing list. To accomplish this, we need your help!


Please contact your local United Way Office or representative and ask if they offer a Directed Donor Program, or a program they have created, to allow for directed donations. If they do, please contact the DBAF and we will assist in completing the application. Each chapter has their own requirements and application process.

Editor's note: The DBAF also participates in many state and federal combined appeal campaigns.  


Please contact your local United Way and ask if they have A Directed Donor Program today!!!

Upcoming Events
Garage Sale for DBA 
May 14, 2011  
502 Rebel Drive
Tupelo, MS
Victoria Boatman

DBA 5K Walk/Run
May 21, 2011
Republic Parks & Recreation Center
Republic, MO
Jacob & Scarlett Buckmaster

Fun Day for DBA 
June 25, 2011
396 Wilson Street
Clinton, MA

Matthew Pulnik & Julie Grady

Friends of DBAF Golf 

Outing & Silent Auction 
September 17, 2011  
Cherokee Hills Golf Club
Valley City, Ohio

Jim and Carol Mancuso


Wristbands Available
Twila Edwards 

Tribute Cards Available
(2 styles)
In honor of...
In memory of...
Dawn Baumgardner

donation donation

DBA Cookbooks Available

Betty Lightner
To download your order form:

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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

Out of This World

by Joanne Drew


Drew family
Photo courtesy of Amy Parrish Photography

My good friend was telling me the other day what activities and camps she was signing her kids up for this summer. I didn't admit to her that I hadn't even thought of what my kids would do this summer. I hadn't because when I plan ahead, I think of Fred's follow-up appointments and labs and tests and hospital stays and transfusion days. Everything else in our lives fills in around that. In this way, living with DBA makes us unlike most everyone we know. And then, aside from how we live with it practically, Mark and I have this constant awareness in the back of our minds of the side effects of DBA; the iron overload, and infection, or eye problems, ear problems, heart problems, growth issues, temper tantrums in the grocery store due, in part, because of low hemoglobin, blood reactions, the thought of BMT, and of course we remember with love those of us who have already earned their angle wings.  These things press on us like a big older neighbor-kid pushing on a bruise.


This is one side of DBA that we all know. But there is another side of DBA whose effects I am actually glad for and very proud of.  For one thing, Fred has a sense of empathy and strength that I think have come solely from his experiences with DBA. He philosophizes about things. A couple of weeks ago while driving home from our last hospital stay, Fred said to me: "The thing about anger is, it doesn't last forever." I turned down the Wiggles song we were listening to and did a double take! Did that really come from my 5-year-old?  Days later when Matilda cried about getting her vaccinations, Fred told her, "What does Snow White do when she's scared?  She sings!" And he sang to her.  And then a couple days ago, Dawn and I were talking on the phone and I said (sort of half joking, but sort of not) that I felt that Fred would probably never have issues with teenage drinking because he can't stand the smell of the alcohol wipes and because it's what the lab techs and nurses and doctors' hands smell like when they come near him.


But what strikes me most is that Fred has earned a very unique perspective on life. He loves space and idolizes astronauts, partly I suppose because they are cool, but mostly because he identifies with astronauts in a very real way.  He knows that before astronauts go into space they have to go to doctors appointments and have a lot of needle sticks and medical tests. He knows that John Glenn had his blood drawn ten times while he was on the Discovery Mission and that he was hooked up to a special monitor every night while he slept. He has seen the movie Apollo 13 where Tom Hanks, portraying Jim Lovell, gets so frustrated with the biosensors taped to his skin that he rips them off his chest midflight.  Fred even knows about "Astronaut Anemia," a condition in which, in zero gravity, the bone marrow stops making red cells.  Because of these things so much like his own, Fred believes that going into space is not only possible in his life experience, it is inevitable; like learning to tie his shoes and write his name. This is the essence of Fred's faith. And it has been Fred's big lesson to Mark and me: just as we have no doubt that one day he will write his name, we have faith that one day he will no longer battle DBA.


We had the honor two weeks ago of meeting with John and Annie Glenn.  It was a huge thrill for all of us. And toward the end of our visit Annie said to me, "I can see that you are very good parents."  She meant it honestly and coming from her it was the single best compliment I think I have ever had.  And I realize writing this, that yes, we are very good parents. All of us. All of us who live with DBA are very good parents, indeed.

Take the Challenge ~ Show Us Your Logo 

 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.

 Led by the artistic talents of Trevor Mancuso,  our DBA families put their hands and hearts into this project. This beautifully decorated bookcase was created at Camp Sunshine 2010. Look closely, our skillfully hand-painted logo adorns the top shelf. Thanks for the memories Camp Sunshine!  Great job Trevor and campers!
Here's the challenge:  we'd like to see how many places we caDBAF  Logon 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 

Happy Mother's Day 

Mothers Day1

The Diamond Blackfan Anemia Foundation  extends our sincerest wishes to all the extraordinary moms, grandmothers, aunts, sisters, friends, and all the special women who touch the lives of our DBA families.  We recognize and applaud the most difficult and most rewarding job you do.  

Do you know about our Mother's to Father's Day Challenge? Click here to learn more Celebrate DBA Moms & Dads.  

Where Are You Now?

Help us to help you! Some information is best delivered to your home address. We are currently in the process of verifying our patients' and families' contact information.  If you have not yet done so, please take a moment to visit our secure website and complete the registration form. This information will allow us to keep you updated and informed. Thank you for your cooperation. 

If you have any questions regarding the status of your information, please contact Dawn Baumgardner at 

 Journal Club 
Steve Ellis
Steven R. Ellis, PhD
Research Directo

This month's Journal Club is, in part, a literary piece including a biography of one of the authors of the manuscript under consideration.  This biography will be in the Hellenist tradition, focusing on big picture items, rather than a detailed chronology of a person's life.  Is this biography of one of the elder statesmen (or women) in the DBA field?  Actually not, this person is in his late 20's early 30's max, but has already accomplished much at this young age.  The subject of this biography is Dr. Johan Flygare, physician/scientist by choice, Swede by birth.  When I entered the DBA field in the mid 2000's, Johan was already making a name for himself as a graduate student in Dr. Stefan Karlsson's lab at Lund University in Sweden.  Their group had created one of the more sophisticated cellular models of DBA.  During this period, Johan also spent a brief period in my laboratory and together with Dr. Anna Aspeci, who was visiting from Irma Dianzani's lab in Italy, we were able to show a ribosome biogenesis defect in cells from DBA patients.  In the late 2000's Johan had to return to clinical training, but after receiving his MD he returned to the Karlsson lab briefly before entering the laboratory of Dr. Harvey Lodish at the Whitehead Institute in Boston.  It is a manuscript stemming from his time in the Lodish lab that is the subject of this Journal Club.  This manuscript has substantial implications for the development of improved therapies for Diamond Blackfan anemia.


The manuscript (Flygare et al) published in Blood (2011) 117:3435-3444 is entitled "HIF1α synergizes with glucocorticoids to promote BFU-E progenitor self-renewal".  As you are all aware, steroids are a therapeutic option for DBA, but come with a number of potential complications. The work by Flygare and colleagues shows that drugs that increase the amount of the protein HIF1α work together with glucocorticoids to stimulate the production of erythorid progenitor cells found in reduced amounts in DBA patients.  These studies suggest that it might be possible someday to treat DBA with reduced steroid doses, or eliminate exogenous steroids altogether using drugs that increase HIF1α levels.  Much still remains to be worked out before this approach will translate to the clinic, but it is encouraging to note that drugs targeting HIF prolyl hydroxylases are currently being considered as alternative treatments for EPO-responsive anemias so their toxicity profiles and other pharmacological properties are currently being examined (Muchnik & Kaplan).


Let us turn our attention back to the Flygare manuscript.  The study begins by describing a new technique to isolate the hematopoietic progenitor cell populations thought to be primarily affected in DBA.  They were then able to show that it is the BFU-E progenitor cells that are responsive to glucorticoids, stimulating their self renewal and thereby increasing the amount of erythroblasts that can be derived from individual BFU-Es approximately 40-fold.  To understand how glucocorticoids were having this effect, Flygare and colleagues examined changes in gene expression induced by glucocorticoids.  Somewhat surprisingly, the authors found that many of the genes upregulated by glucocorticoids contained DNA sequence signatures characteristic of genes regulated by the protein HIF1α.  HIF1α regulates gene expression in response to low oxygen concentrations.  A role for HIF1α in erythropoiesis has been known for some time as a regulator of erythropoietin (EPO), which makes a great deal of sense, because if oxygen concentrations are low, a reasonable response would be to induce erythropoietin expression and make more red blood cells.  HIF1α itself is regulated by a family of enzymes known as HIF prolyl hydroxylases, which use molecular oxygen to label the HIF1α protein for degradation.  When oxygen partial pressures are low, the HIF prolyl hydroxylases targeting HIF1α are inhibited, leading to higher levels of HIF1α which in turn stimulate erythropoietin production.  The surprise in the Flygare manuscript however, was that HIF1α also appears to be involved in inducing erythropoiesis at an earlier stage upstream of EPO, acting on BFU-E's to stimulate their self-renewal.


The authors reasoned that by inhibiting the HIF prolyl hydroxylases targeting HIF1α they could potentially increase HIF1α levels and stimulate erythropoiesis at the progenitor level.  Moreover, they felt that glucocorticoids and prolyl hydroxylase inhibitors might work together or at least show some partial overlap in stimulating erythropoiesis at the progenitor stage.  When put to the test, they were able to show that a drug targeting HIF prolyl hydroxylases enhanced the effect of glucocorticoids in stimulating BFU-E's by about 7 fold.  Thus, the two drugs have a synergistic effect in inducing the production of CFU-E's and erythroblasts from BFU-E's. 


What has all this to do with DBA?  Plenty, in fact.  To quote the authors, "A group of patients who directly could benefit from the CFU-E-promoting effect of PHIs [Prolyl Hydroxylase Inhibitors] are those with the red cell progenitor disorder DBA."  The results from Flygare et al. suggest that with the synergistic effect seen with prolyl hydroxylase inhibitors it may be possible to reduce steroid concentrations in treating DBA patients or possibly eliminate exogenous steroids altogether through the ability of prolyl hydroxylase inhibitors to synergize with endogenous levels of steroids found in DBA patients. 


So is there a downside to all of this?  Well, yes; inhibiting prolyl hydroxylases that target HIF1α for degradation could lead to an enhanced risk of cancer.  Once marked for degradation by prolyl hydroxylases, another protein is necessary to direct the actual degradation of HIF1α.  A genetic deficiency of this other protein leads to von Hippel-Lindau syndrome, a strong cancer predisposition syndrome.  The rationale for this increased incidence of cancer is in part, that tumors are frequently hypoxic (reduced oxygen supply) and need HIF1α expression to counteract the hypoxia.  Thus, promoting HIF1α expression by using prolyl hydroxylase inhibitors could in principle lead to an increased risk for cancer.  While there is certainly cause for proceeding with caution on the potential use of prolyl hydroxylase inhibitors as a treatment option for DBA, these studies nevertheless open a new window of opportunity for improved treatment options for patients with DBA.


One final note in this rather lengthy journal club is that Dr. Flygare has been supported by the DBA Foundation at various points in his career.  He is transitioning from the Lodish lab to begin his own laboratory at the same Institute as that of Stefan Karlsson in Lund Sweden.  One of the proposals currently under review for funding from the DBA Foundation is from Dr. Flygare as he starts this new phase of an extremely productive career.                            
Flygare J, Rayon Estrada V, Shin C, Gupta S, Lodish HF HIF1alpha
synergizes with glucocorticoids to promote BFU-E progenitor self-renewal. Blood 117(12): 3435-3444


Muchnik E, Kaplan J HIF prolyl hydroxylase inhibitors for anemia. Expert Opin Investig Drugs 20(5): 645-656