Leading Research in New Targeted Therapies for Leukemia / Lymphoma
Research initiatives and collaborations in the Leukemia / Lymphoma Program at Cincinnati Children's Hospital Medical Center integrate with the Blood / Marrow Transplantation Program, the Experimental Hematology research focus programs of Leukemia Biology and Signaling, and the Ohio State University Comprehensive Cancer Center Experimental Therapeutics program. In addition, intramural Cincinnati Children's research initiatives are integrated with the departments of:
National Cancer Institute Pediatric Phase I Consortium
The National Cancer Institute Pediatric Phase I Consortium is the primary pipeline for the rapid and efficient development of new anticancer therapeutics in children through the Cancer Treatment Evaluation Program (CTEP). Cincinnati Children's Cancer Center is an active participating program in the NCI Consortium.
- The focus of John P. Perentesis, MD, FAAP, is on new leukemia drug development and he chairs the Children's Oncology Group Myeloid Leukemia Relapse Committee. This committee is introducing bortezomib and lestaurtinib, clofarabine / Ara-C and other agents into pediatric leukemia therapeutics. These activities are also facilitated by Dr. Perentesis' role on the NCI Investigational Drug Steering Committee (IDSC), a new initiative which works with NCI/CTEP to identify and prioritize new anticancer drug development for both children and adults.
- Cincinnati Children's and the Ohio State University Comprehensive Cancer Center are collaborating on a new Pediatric Phase I Study of Flavopiridol in Refractory and Relapsed pediatric patients with leukemia.
- In close interaction with Drs. Michael Grever and John Byrd of the OSU-CCC Experimental Therapeutic Program, Drs. Sonata Jodele and John Perentesis have obtained CTEP approval and are opening a pediatric stratum of the OSU-CCC phase I study of flavopiridol. The development of the pediatric stratum of this regimen is being used as a model for additional development of other technically-demanding OSU-CCC pediatric phase I studies.
- Stella M. Davies, MBBS, PhD, MRCP, is leading a national trial seeking to identify the host factors for genetic susceptibility as well as pharmacogenetic factors influencing outcomes and toxicity in pediatric leukemia therapy. The trial is funded through an NIH R01 grant and is integrated into all national COG acute lymphoblastic leukemia therapy studies.
- Dr. Perentesis leads an effort to identify molecular mechanisms in the etiology and evolution of leukemia in children with Down syndrome. This NIH R01 funded effort is incorporate into national COG studies of transient myeloproliferative disorder and acute leukemia occurring in children with Down syndrome. The study utilizes detailed analyses of hematopoiesis, oncogene mutations, geno-toxicity and gene expression assays in high risk populations. His laboratory is also studying the pharmacogenetic and pharmacodynamic factors influencing early outcomes in patients with Hodgkin's disease. The study objective is to identify the large subset of patients who either do not require full dose intensity for the favorable outcome or who are genetically susceptible to complications and late effects.
- Mary Sutton, MD, is examining the neuropsychological sequelae of leukemia therapy.
- David Pruitt, MD is developing a study to evaluate the incidence of steroid myopathy and functional consequences in a pilot study of Cincinnati Children's leukemia patients.
- Yi Zheng, PhD, in the Division of Experimental Hematology, is developing the targeted Rac Inhibitor NSC 23776 in leukemia. The small molecule drug targets and inhibits oncogenic signaling through Rac. The Rho GTPase inhibitor has been shown to be active against leukemias. Further molecular refinement and human trials are currently being developed.
- The laboratory of James C. Mulloy, PhD, has developed novel leukemia models to study the mechanism of drug resistance associated with relapse in acute lymphoid and myeloid leukemia. These models are being used to define the nature of the leukemia stem cell and to examine the differences in drug sensitivities between leukemias and the normal blood/bone marrow stem cell. This unique model of human leukemia in the test tube is being used for testing new drug therapies and has the potential to become a powerful screening tool in the search for effective drugs that will target the leukemia stem cell.
- The laboratory of Paul R. Andreassen, PhD is generating synergistic interactions between basic scientists and clinicians to facilitate the translation of laboratory observations in Fanconi anemia into the clinic. Dr. Andreassen’s scientific focus is on the dissection of the components of the Fanconi Anemia. His work is also focused on developing new therapies for this disease, and for leukemia with abnormalities of the Fanconi Anemia genes.
- The focus of the H. Leighton Grimes, PhD laboratory is to understand the genetic programs that control the causes and growth of leukemias. His work is defining key growth-factor – related genes that define different subsets of myeloid and lymphoid leukemias, and targeted therapies that may interrupt these pathways.
