Therapy-related leukemia is a late complication of treatment with cytotoxic drugs or irradiation. There are at least 3 distinctive clinicopathological and cytogenetic syndromes. One of the special features of this Program Project is that the 4 individual projects are absolutely dependent upon patient material, since most of the questions to be addressed arise from the nature of individual patient responses to cytotoxic therapy. That is, why do some patients develop secondary leukemia, and others not? The Patient Access, Data Management, Statistical Analysis, and Tissue Culture Core (A) has the 4-fold missions of subject recruitment and informed consent, specimen acquisition and storage, data management and statistical collaboration, and the generation of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. These functions are critical to the successful completion of the proposed investigations in each of the 4 projects and necessary to support and link together the results that come from the various laboratories. In this way, unique patient resources are shared in the most productive manner. Core A is highly integrated with all 4 projects, and this collaborative work has resulted in 21 original articles and abstracts during the past grant period. To provide an orderly access to patient material and to maintain records, we propose to continue our Core A component to manage these functions as it has for the past 22 years. Core A insures that appropriate blood and marrow specimens are obtained prospectively for the Cancer Cytogenetics Laboratory from new patients with t-MDS/t-AML, AML de novo, or primary MDS. Research subjects sign Informed Consent forms that are reviewed and approved by the University of Chicago Institutional Review Board annually. After collection, the clinical specimens are logged in, processed appropriately, and then either stored or delivered to the individual projects. Requests from each project PI for specific clinical materials (normal or malignant blood or marrow cells, DNA from buccal swabs, or cell lines from specific patients or family members) are received by Core A. Requests from program investigators have the highest priority, but samples have also been shared with other cancer researchers both at the University of Chicago and elsewhere. Core A also has the responsibility for generating an immortalized, lymphoblastoid cell line from each patient with a primary or therapy-related leukemia. Thus, both normal and malignant cells from each patient are stored in the Core facility. These resources allow us to study the non-malignant cells and germline DNA from both living and deceased patients with t-AML. Patient confidentiality is appropriately protected. Data forms are kept secured. Case numbers are assigned;names are not used in publications. Research data are not placed in patients'medical records. Inventories of cells and research data are maintained in confidential electronic files under password security. The database is automatically backed up on a daily basis;tapes are made and stored off site for further protection. There is no dial-in access to the database, and anti-virus screens are continuously employed on the network. Access is restricted to 4 individuals in Core A, each of whom has completed the required course in Human Subjects Protection coordinated by the University of Chicago Institutional Review Board.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA040046-25
Application #
8381382
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
25
Fiscal Year
2012
Total Cost
$295,837
Indirect Cost
$67,889
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Clay-Gilmour, Alyssa I; Hahn, Theresa; Preus, Leah M et al. (2017) Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex. Blood Adv 1:1717-1728
Churpek, Jane E; Marquez, Rafael; Neistadt, Barbara et al. (2016) Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia. Cancer 122:304-11
Stoddart, Angela; Qian, Zhijian; Fernald, Anthony A et al. (2016) Retroviral insertional mutagenesis identifies the del(5q) genes, CXXC5, TIFAB and ETF1, as well as the Wnt pathway, as potential targets in del(5q) myeloid neoplasms. Haematologica 101:e232-6
Sasaki, Mark M; Skol, Andrew D; Hungate, Eric A et al. (2016) Whole-exome Sequence Analysis Implicates Rare Il17REL Variants in Familial and Sporadic Inflammatory Bowel Disease. Inflamm Bowel Dis 22:20-7
Shankar, Sunita; Pitchiaya, Sethuramasundaram; Malik, Rohit et al. (2016) KRAS Engages AGO2 to Enhance Cellular Transformation. Cell Rep 14:1448-1461
Hungate, Eric A; Vora, Sapana R; Gamazon, Eric R et al. (2016) A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology. Nat Commun 7:10635
Vasanthakumar, Aparna; Arnovitz, Stephen; Marquez, Rafael et al. (2016) Brca1 deficiency causes bone marrow failure and spontaneous hematologic malignancies in mice. Blood 127:310-3
Sasaki, Mark M; Skol, Andrew D; Bao, Riyue et al. (2015) Integrated genomic analysis suggests MLL3 is a novel candidate susceptibility gene for familial nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev 24:1222-8
Wong, Jasmine C; Weinfurtner, Kelley M; Alzamora, Maria Del Pilar et al. (2015) Functional evidence implicating chromosome 7q22 haploinsufficiency in myelodysplastic syndrome pathogenesis. Elife 4:
Sundaravel, Sriram; Duggan, Ryan; Bhagat, Tushar et al. (2015) Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes. Proc Natl Acad Sci U S A 112:E6359-68

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