Kendall & Taylor Atkinsonfoundation

TO RAISE MONEY FOR CHARITABLE ALLOCATION.

ALLOCATIONS WERE MADE TO THE FANCONI ANEMIA RESEARCH FUND TO SUPPORT MEDICAL, SCIENTIFIC AND TREATMENT RESEARCH OF FANCONI ANEMIA AND ITS RELATED CANCERS: *$60,000 WAS ALLOCATED TO FUND FURTHER RESEARCH ENTITLED GELFITNIB/AFATNIB THERAPY FOR HEAD AND NECK SQUAMOUS CELL CARCINOMA IN FANCONI ANEMIA. THE RESEARCH IS BEING CONDUCTED BY JORDI MINGUILLON, PHD AND JORDI SURRALLES PHD, SPAIN. THE GOAL OF THIS RESEARCH IS TO DEVELOP NEW THERAPIES TO PREVENT, CURE OR AMELIORATE FA HEAD AND NECK SQUAMOUS CELL CARCINOMA. BEYOND SURGERY THERE IS CURRENTLY NO EFFECTIVE THERAPY TO TREAT PEOPLE WITH FA WHO DEVELOP SOLID TUMORS. RESEARCHERS WILL EXAMINE TWO CURRENTLY FDA-APPROVED DRUGS AS A POTENTIAL FOR SOLID TUMORS IN FA AND DEVELOP A MULTICENTER INTERNATIONAL CLINICAL TRIAL FOR FA PATIENTS.*$71,118 WAS ALLOCATED TO FULLY FUND RESEARCH ENTITLED FANCONI ANEMIA ASSOCIATED NEUROLOGICAL SYNDROME-A SEARCH FOR A CAUSE WITH ADVANCED TECHNOLOGIES. THE RESEARCH IS BEING CONDUCTED BY INVESTIGATORS PRASHANTH RAMACHANDRAN, MD AND MICHAEL WILSON, MD AND COLLABORATOR EUNIKE VELLEUR, MD AT THE UNIVERSITY OF CALIFORNIA SAN FRANCISCO. FANCONI ANEMIA ASSOCIATED NEUROLOGICAL SYNDROME (FANS) IS A NOVEL AND PROGRESSIVE CONDITION THAT AFFECTS A SUBSET OF PATIENTS WITH FANCONI ANEMIA (FA). THE CONDITION LEADS TO SIGNIFICANT DISABILITY, AND CURRENTLY THERE IS NO KNOWN CAUSE, AND A VARIETY OF EMPIRIC TREATMENTS HAVE NOT BEEN EFFECTIVE. FANS IS CHARACTERIZED BY CONTRAST ENHANCING AND CALCIFIC LESIONS ON BRAIN MRI, WITH BRAIN BIOPSIES DEMONSTRATING NECROSIS, GLIOSIS AND VASCULOPATHY. THE CLINICAL COURSE IS PROGRESSIVE, WITH SLOW ACCUMULATION OF LESIONS AND DISABILITY, PUNCTURED BY DEVELOPMENT OF LARGE CONTRAST ENHANCING LESIONS WITH SIGNIFICANT EDEMA. CURRENTLY, THERE ARE SEVERAL HYPOTHESES FOR THE UNDERLYING CAUSE INCLUDING INFECTIOUS, AUTOIMMUNE, GENETIC AND VASCULAR ETIOLOGIES. WITH NO DEFINITIVE ETIOLOGY HAVING BEEN IDENTIFIED, APPROPRIATE MANAGEMENT OF PATIENTS REMAINS UNCLEAR. CHARACTERIZING THE CLINICAL PHENOTYPE OF FANS AND UNDERLYING PATHOLOGICAL MECHANISM(S) WILL PROVIDE THENECESSARY STEPS TOWARDS DEVELOPING PREVENTION AND TREATMENT OPTIONS FOR PATIENTS WITH FANS.*$5,882 WAS ALLOCATED TO PARTIALLY FUND RESEARCH ENTITLED UNDERSTANDING CLONAL HEMATOPOIESIS IN FANCONI ANEMIA TO IMPROVE PATIENT SURVEILLANCE STRATEGIES. THIS RESEARCH IS BEING CONDUCTED BY GRANT ROWE, MD, PHD AT BOSTON'S CHILDREN'S HOSPITAL.CLONAL HEMATOPOIESIS (CH) DEVELOPS AS A RESULT OF ACCUMULATION OF CYTOGENETIC ABNORMALITIES IN HEMATOPOIETIC STEM CELLS (HSCS) AND IS A PRECURSOR TO MYELODYSPLASTIC SYNDROME (MDS) OR ACUTE MYELOID LEUKEMIA (AML). INDIVIDUALS WITH BONE MARROW FAILURE (BMF) DISORDERS SUCH AS FANCONI ANEMIA (FA) EXPERIENCE ACCELERATED CH WITH ONSET AS SOON AS THE FIRST FEW YEARS OF LIFE RESULTING IN A VERY HIGH RISK OF DEVELOPING MDS AND AML AS A TEENAGER OR YOUNG ADULT. FA PATIENTS ARE ROUTINELY SCREENED FOR THE PRESENCE OF CH BY ASSAYING FOR SOMATIC MUTATIONS OR CYTOGENETIC ALTERATIONS WITHIN BONE MARROW CELLS. THE IDENTIFICATION OF CH IN FA PATIENTS HAS PROFOUND IMPACT ON THEIR CARE AS THIS OFTEN LEADS TO IMMEDIATE ALLOGENEIC STEM CELL TRANSPLANTATION (SCT) AND CONSEQUENT EXPOSURE TO THE SHORT- AND LONG-TERM TOXICITIES OF SCT. DESPITE THE WELL-KNOWN RISK OF AML IN FA, CH IN FA IS NOT WELL UNDERSTOOD, WITH ONLY A FEW EXISTING PUBLICATIONS DESCRIBING THE SOMATIC MUTATIONAL SPECTRUM OF CLONAL MYELOID DISORDERS IN FA. MOREOVER, THE MECHANISTIC ROLE OF RECURRENT CYTOGENETIC ABNORMALITIES AND POINT MUTATIONS IN OVERCOMING HSC SENESCENCE AND PROMOTING THE EXPANSION OF FA HSCS AND CONFERRING MDS/AML RISK IS ENTIRELY UNKNOWN. DELINEATION OF THE CELLULAR AND MOLECULAR EFFECTS OF GENETIC ALTERATIONS RECURRENTLY SEEN IN FA CH ON HSC WILL TRANSLATE INTO RISK STRATIFICATION OF FA CH PATIENTS, WITH THE POTENTIAL TO DIRECTLY IMPACT CLINICAL MANAGEMENT, INCLUDING THE USE OF SCT.