LEUKEMIAS
Retrospective analyses of AML are able to provide limited recreation of the processes involved in the evolution of the disease and its response to therapy. By combining the well-validated animal models of AML proposed here with clonal tracking methods, high resolution in vivo microscopy and unique indicators of in vivo cell functions, we will be able to capture a multi-parametric quantitative assessment of AML over time and test the relationships of those parameters to chemotherapy response. This will generate a highly novel and rich dataset for computational analysis. Integration of this data with novel mathematical modeling will create algorithms to enhance chemotherapy response that will be tested and iteratively refined. We have assembled an exceptionally innovative team with a proven track record in interdisciplinary research to perform these studies. Collectively, this assembly of expertise, tools, data and analytic methods are unique and will enable innovative, rationally designed strategies to improve outcomes in AML.
LITERATURE CITED 1. American Cancer Society, editor. Cancer Facts and Figures 2014. American Cancer Society, 2014; 2014; Atlanta, Ga, USA. 2. Klco JM, Spencer DH, Miller CA, Griffith M, Lamprecht TL, O'Laughlin M, Fronick C, Magrini V, Demeter RT, Fulton RS, Eades WC, Link DC, Graubert TA, Walter MJ, Mardis ER, Dipersio JF, Wilson RK, Ley TJ. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia. Cancer Cell. 2014;25(3):379-92. 3. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, McMichael JF, Wallis JW, Lu C, Shen D, Harris CC, Dooling DJ, Fulton RS, Fulton LL, Chen K, Schmidt H, Kalicki-Veizer J, Magrini VJ, Cook L, McGrath SD, Vickery TL, Wendl MC, Heath S, Watson MA, Link DC, Tomasson MH, Shannon WD, Payton JE, Kulkarni S, Westervelt P, Walter MJ, Graubert TA, Mardis ER, Wilson RK, DiPersio JF. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506-10.
|