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SUMMARY OF RESEARCH FUNDED BY BBC

2014 PROGRESS UPDATE:

Blue Butterfly Campaign donated $45,000 to Dr. Peter Kurre’s Research at Doernbecher Children’s Hospital, which is focused on using simple blood draws for early non-invasive diagnosis of Acute Myeloid Leukemia (AML). BBC funds allowed Dr. Kurre to purchase the instrument needed to identify special markers released by leukemic cells in the blood making early detection and cancer relapse easier to recognize. This in turn enabled Dr. Kurre and his team to continue the critical research moving their studies closer to helping the kids with AML. 

Almost half of all children with AML continue to suffer relapses of the disease. Currently, detecting a relapse requires drilling into the hip for bone marrow sampling. With this practice, the relapsed leukemia is detected too late causing children to need intense chemotherapy, radiation and stem cell transplantation treatments. In other cases, the reoccurrence of leukemia goes undetected. This current approach of bone marrow aspiration is not only painful and invasive, but only successful in detecting the leukemia in one of every 40 procedures performed. 

For more information about Dr. Peter Kurre’s research, click here 
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JUNE 2013 PROGRESS UPDATE:
Research By Dr. Stella Davies and Dr. Christine Phillips 
 
SIGNIFICANCE

Progress in treating childhood cancer has been achieved with more than 30 years of clinical trials that have applied the discipline of giving uniform therapy to all children to allow progress to be made. To make further progress, such that all children with AML are cured, we now need to understand the variations in genetics in each child to allow us to individualize therapy for the children not cured with current regimens.  Knowledge of genetic characteristics that predict either excessive side effects, or inadequate therapy (relapse) at the time of diagnose will allow better selection of therapy and will improve survival. 

PROGRESS:

Since last year, we have made significant progress on my project outlined in the research plan. Aliquots of DNA which had been extracted many years prior were stored and available in sufficient quantities in our laboratory for 346 patients. Additionally, we were able to acquire DNA for an additional 115 patients from the Children’s Oncology Group lab that stores the patient samples.  We have processed and prepared DNA from all of these patient samples and have adequate numbers to answer the research questions.

We tested the OpenArray chips which are designed to allow us to look at many gene variants at one time by first running the tests on normal controls (obtained from normal blood donors). We have now completed this same process on the patient DNA.  All samples have now been genotyped (or analyzed for specific gene variants) at 128 loci using OpenArray platform. This platform was successful for the large majority of patient samples, with a failure rate of only 4.9% (23 of 461) for patient samples.  

PROGRESS SINCE LAST UPDATE:

Twelve of the gene variants were not able to be analyzed using the Open Array technology due to limitations of the prepared chips and need to be done one variant at a time for all of the samples. Our current laboratory focus has been designing of probe/primer sets and performing single SNP Taqman to analyze the patient DNA at these loci.  Since our last update, I have completed further genotyping of the 450 samples for two additional variants, now completing half the number of required assays that need to be done as individual tests.  We anticipate completion of the laboratory work in the next couple months.  We have submitted a revised request for data set from Childrens Oncology Group that outlines the clinical data the we need to determine if our genetic model predicts how children respond to the drug cytarabine.  



APRIL 2013 PROGRESS UPDATE:
  
Work is continuing on the gene testing, which is close to completion, and clinical data are being prepared at the Children's Oncology group for the analysis of the genetic data. Our current laboratory focus has been the designing of probe/primer sets and performing single SNP Taqman to analyze the patient DNA at these loci.  In the last two months, Dr Phillips has performed manual genotyping of the 450 samples at four of the 12 different variants that needed to be completed as separate assays. We anticipate completion of the laboratory work in the next two to three months. We are continuing to work on refining the questions that can be best incorporated into our complex analysis that our statisticians will help perform. We expect this to be the most complex part of this research project. Additionally, we have contacted the Children's Oncology Group to begin working on obtaining DNA from the successor clinical trial so that we can validate any findings from this study in a separate group of patients.  This step is very important to determine whether or not the findings of our research are clinically significant to patients.

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JANUARY 2013 PROGRESS UPDATE

BACKGROUND

Approximately 50% of children with acute myelogenous leukemia (AML) will become long-term survivors after treatment with chemotherapy.  One drug, cytosine arabinoside (cytarabine or Ara-C), is a key element in achieving cure, and has been tested in serial clinical trials in combination with other drugs to achieve the successes seen with current therapy.  Despite this progress, and despite the administration of uniform drug regimens in well-conducted national clinical trials, a proportion of children with AML still die from toxic side effects of therapy, and a larger number still relapse.  Understanding the basis for this inter-individual variation in response to therapy will help extend cure to these groups of patients.

SIGNIFICANCE

Progress in treating childhood cancer has been achieved with more than 30 years of clinical trials that have applied the discipline of giving uniform therapy to all children to allow progress to be made. To make further progress, such that all children with AML are cured, we now need to understand the variations in genetics in each child to allow us to individualize therapy for the children not cured with current regimens.  Knowledge of genetic characteristics that predict either excessive side effects, or inadequate therapy (relapse) at the time of diagnose will allow better selection of therapy and will improve survival. 

The principle investigator on this project, Dr. Christine Phillips, was just awarded the AACR-FNAB Translational Cancer Research Career Development Award which will provide her with $100,000 in salary over the next two years.

Dr. Stella Davies reports that the laboratory studies are largely done, and the next step is matching up the laboratory findings with the clinical information, which is the most exciting but perhaps the hardest part of the study.

Funding for 2016 -
​Dr. Kurre Research

Current treatment for children diagnosed with acute myeloid leukemia (AML) leads to the rapid clearance of leukemia (blood cancer) cells from the bloodstream. Yet, up to 40% of children still suffer from disease recurrence.  We now understand that the bone marrow serves as a sanctuary, protecting residual leukemia cells that give rise to drug-resistance and relapse.
Our research is therefore focused the cells (termed stroma) in the bone marrow of AML patients that are responsible for the emergence of drug resistance. Our long term goal is to develop treatments that overcome stroma-enforced drug resistance. 
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Not until the role of the bone marrow in sustaining residual leukemia cells is understood, will children with AML experience the full benefits of next-generation “precision medicine” and the “personalized treatment” that is so successful in treating adult patients with leukemia.

Fund Allocation

The 2012 BBC donation of $50,000 were used as follows:

• $20,000 ~  Gene specific primers (used to test genes of children with AML)
• $6,200  ~  Plastic ware (test tubes, pipettes, etc) 
• $10,000  ~ Analysis reagents (chemicals, enzymes, etc)
• $ 4,800   ~ Miscellaneous lab supplies (liquid nitrogen, dry ice, data storage, etc)
• $10,000 ~ Remainder of the BBC funds will be used in the next three months for supplies
  

Additional Study Update

Dr. Davies shares information on an additional study which has personal relevance to the Dearborn family since Max had AML with the monosomy 7 mutation. Researchers in Dr. Davies’ group are continuing to work on understanding why very young children sometimes get monosomy 7.  They have been able to show that when monosomy 7 arises in very young children the abnormality arises in a very early stem cell;  in at least some cases, the abnormality happens before the baby is born because they can find the abnormality in their blood at birth.  They are now exploring this further by growing the abnormal cells in special mice, so they can study potential treatments of monosomy 7. They reported their findings on this topic at the American Society of Hematology Annual meeting in Atlanta in December 2012.