Robert Arceci, M.D., Ph.D.

Phone: (410) 502-7519

Categories:

• Pediatric Oncology

Titles

King Fahd Professor of Pediatric Oncology
Professor of Oncology
Professor of Pediatrics

Schools/Degrees

M.D., University of Rochester, Rochester, NY
Ph.D., University of Rochester, Rochester, NY

Training

Resident in Pediatrics, Children's Hospital, Boston, MA

Fellow in Hematology/Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, MA

Certifications

Pediatrics, Pediatric Hematology/Oncology

Clinical Interests

Dr. Arceci's focus is on translational research in pediatric malignancies and on optimizing comprehensive care for children and adolescents with cancer.  He has been particularly involved in the development of novel therapeutic targets and immunotherapies to improve outcomes while reducing adverse side effects in patients with cancer.  He is an internationally know expert in leukemia, transplantation and in histiocytic disorders such as Langerhans Cell Histiocytosis.  He has spearheaded clinical trials testing the ability to reverse multidrug resistance transporters, targeted monoclonal antibody approaches to treatment and signal transduction inhibitors in pediatric patients with leukemia. 

He has served as the chairperson of the Myeloid Leukemia Committee of both the Children's Cancer Group and the Children's Oncology Group.  He also now serves as Vice-Chair of the Children's Oncology Group's Development Therapeutics Committee.  He is one of the founding members of a Pediatric Phase I consortium, called POETIC, which has a primary focus the clinical testing of new agents targeting specific molecular pathways in cancer in children and adolescents.  He has served as an Associate Editor of The Journal of Pediatrics, as the Editor-in-Chief of the Journal of Pediatric Hematology/Oncology and is the Editor of the Pediatric Oncology Section of the Yearbook of Oncology.  He is currently Editor-in-Chief of Pediatric Blood and Cancer. 

Research Summary

Dr. Arceci’s laboratory research is focused on the elucidation of fundamental mechanisms of cell growth, survival and senescence during normal and neoplastic development with the overall goal of identifying novel pathways for therapeutic targeting of leukemia and solid tumors. Active areas of work include:

 

Epigenetic Mechanisms during Development, Cancer Pathogenesis and Senescence

We are investigating basic mechanisms regulating chromatin structure and DNA methylation using biochemical, genetic and knockout murine and zebrafish models. Our laboratory has cloned a novel chromatin remodeling helicase, named PASG, that is involved in genomic methylation critical for regulating the senescence. We are currently investigating the mechanisms by which PASG affects chromatin structure leading to genomic instability and replicative senescence as well as developing models for therapeutic targeting of senescence pathways. This work involves humans as well as mouse and zebrafish model systems.

 

Activating Mutations of the c-KIT Tyrosine Kinase in Leukemia

The role of cytokines and their cognate receptors during normal and neoplastic cell growth, differentiation and programmed cell death is being studied. Current work is focused on defining the signal transduction pathways resulting from activating mutations of the c-KIT tyrosine kinase receptor and identifying therapies to block the survival and drug-resistant mechanisms in leukemias and solid tumors expressing mutant forms of the receptor.

 

Cancer Predisposition Syndromes

Children with inherited bone marrow failure syndromes usually have characteristic physical abnormalities as well as a predisposition to develop both leukemia and solid tumors. We are focused on the identification of a causative gene in one of these syndromes based on the observation of a patient with an inherited chromosome deletion. The identification and functional analysis of this pathway will help us understand mechanisms of bone marrow failure as well as cancer predisposition.

 

Immunotargeted Therapies for Hematologic Malignancies

This area of research involves the translation of targeted immunotherapies for patients with cancer. Studies are directed toward the development of human monoclonal antibody targeting of tumor cells as well as the use of vaccines to generate antitumor responses. We have developed a human monoclonal antibody directed against the CD1a protein, which is expressed on a subset of thymocytes and Langerhans cells. Experimental studies are investigating this antibody in terms of diagnostic scanning, therapeutic targeting, graft versus host disease prevention and the augmentation of cancer vaccine efficacy.

 

Clinical Research 

There are several new initiatives focused on targeted therapy of children and adolescents with cancer and serious blood disorders. For example, efforts are under way to further test novel targeting agents in pediatric patients with leukemia and solid tumors. These efforts include testing monoclonal antibody-targeted therapy in combination with chemotherapy for patients with relapsed acute myelogenous leukemia (AML), as well as antibody-directed therapy for patients with relapsed ALL. The ability to inhibit the farnesylation of RAS and other similarly activated regulatory proteins as a means to treat patients with leukemia, solid tumors and even neurofibromatosis type I is being tested in phase I and phase II trials. Clinical trials with targeted immunotherapy, as well as differentiation directed therapies, are under way.

 

The ability to generate antileukemia cytolytic immune responses is planned for testing in children with AML with a collaborative trial with investigators in medical oncology. The role of reduced-intensity hematopoietic transplantation for the treatment of children with advanced solid tumors, leukemia as well as nonmalignant inherited disorders of the hematopoietic and immune systems will be tested. Preclinical studies using humanized monoclonal antibodies directed against the CD1a antigen, which is present on some leukemias and on the cells causing Langerhans cell histiocytosis, are being done with plans to then test this approach for diagnosis and treatment of patients with these disorders.

 

 

Journal Citations

Dhall G, Finlay JL, Ettinger LJ, Kellie S, Files B, Egeler RM, Arceci RJ.  Analysis of Outcome of Patients With Langerhans Cell Histiocytosis With Central Nervous System Involvement Treated with 2-chlorodeoxyadenosine.  Pediatric Blood and Cancer.  50(1):72-9; 2008.

Bechan G, Meeker A, DeMarzo AM, Racke F, Jaffe R, Sugar E, Arceci RJ. Telomere length shortening in Langerhans Cell Histiocytosis. British Journal of Hematology, 140: 420-428; 2008

Aplenc R, Alonzo T, Gerbing R, Meshinchi S, Lange B, Smith FO, Wells R, Bernstein I, Sievers E and Arceci RJ.  Safety and Efficacy of Gemtuzumab Ozogamicin in Combination with Chemotherapy for Pediatric Acute Myeloid Leukemia.  J of Clinical Oncology. 26: 2390-2396; 2008.

Noronha, S., Farrar, J.E., Alonzo, T.A., Gerbing, R.B., Lacayo, N.J., Dahl, G.V., Ravindranath, Y., Arceci, R.J. and Loeb, D.M., WT1 expression at diagnosis does not predict survival in pediatric AML: A report from the Children’s Oncology Group (Pediatric Blood and Cancer, In Press).

 

Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC Jr, Meltzer P, Esposito D, Beggs AH, Schneider HE, Grabowska A, Ball S, Niewiadomska E, Sieff  CA, Vlachos A, Atsidaftos E, Ellis SR, Lipton JM, Gazda H, Arceci RJ.  Abnormalities of the Large Ribosomal Subunit Protein, Rpl35A, in Diamond-Blackfan Anemia.  Blood.  112(5):1582-92; 2008.

Suzuki T, Farrar JE, Yegnasubramanian S, Zahed M, Suzuki N, Arceci RJ. Stable Knockdown of PASG Enhances DNA Demethylation but does not Accelerate Cellular Senescence in TIG-7 Human Fibroblasts.  Epigenetics.  3: 281-291; 2008.

Moore JP, Farrar J, Arceci RJ, Liu J M, Ellis SR, Distinct Ribosome Maturation Defects in Yeast Models for Diamond Blackfan Anemia and Shwachman Diamond Syndromes (Hematologica, August 27, 2009 online publication)


Arceci, R.J. (2008). Pediatric Blood & Cancer: the first 5 years. Pediatr Blood Cancer 51, 581-583.

Arceci, R.J. (2008). When T cells and macrophages do not talk: the hemophagocytic syndromes. Curr Opin Hematol 15, 359-367.

 

Bechan, G.I., Meeker, A.K., De Marzo, A.M., Racke, F., Jaffe, R., Sugar, E., and Arceci, R.J. (2008). Telomere length shortening in Langerhans cell histiocytosis. Br J Haematol 140, 420-428.

 

Suzuki, T., Farrar, J.E., Yegnasubramanian, S., Zahed, M., Suzuki, N., and Arceci, R.J. (2008). Stable knockdown of PASG enhances DNA demethylation but does not accelerate cellular senescence in TIG-7 human fibroblasts. Epigenetics 3, 281-291. 

Appelbaum, F. R., D. Rosenblum, R. J. Arceci, W. L. Carroll, P. P. Breitfeld, S. J. Forman, R. A. Larson, S. J. Lee, S. B. Murphy, S. O'Brien, J. Radich, N. S. Scher, F. O. Smith, R. M. Stone, and M. S. Tallman. 2007. End points to establish the efficacy of new agents in the treatment of acute leukemia. Blood 109:1810-6.

 

Bagatell, R., L. Gore, M. J. Egorin, R. Ho, G. Heller, N. Boucher, E. G. Zuhowski, J. A. Whitlock, S. P. Hunger, A. Narendran, H. M. Katzenstein, R. J. Arceci, J. Boklan, C. E. Herzog, L. Whitesell, S. P. Ivy, and T. M. Trippett. 2007.

Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study. Clin Cancer Res 13:1783-8.

 

Barbaric, D., T. A. Alonzo, R. B. Gerbing, S. Meshinchi, N. A. Heerema, D. R. Barnard, B. J. Lange, W. G. Woods, R. J. Arceci, and F. O. Smith. 2007. Minimally differentiated acute myeloid leukemia (FAB AML-M0) is associated with an adverse outcome in children: a report from the Children's Oncology Group, studies CCG-2891 and CCG-2961. Blood 109:2314-21.

 

Brown, P., E. McIntyre, R. Rau, S. Meshinchi, N. Lacayo, G. Dahl, T. A. Alonzo, M. Chang, R. J. Arceci, and D. Small. 2007. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 110:979-85.

 

Dhall, G., J. L. Finlay, I. J. Dunkel, L. J. Ettinger, S. J. Kellie, J. C. Allen, R. M. Egeler, and R. J. Arceci. 2008. Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine. Pediatr Blood Cancer 50:72-9.

 

Lange, B. J., F. O. Smith, J. Feusner, D. Barnard, P. Dinndorf, S. Feig, N. A. Heerema, C. Arndt, R. J. Arceci, N. Seibel, M. Weiman, K. Dusenbery, K. Shannon, S. Luna-Fineman, R. B. Gerbing, and T. A. Alonzo. 2008. Outcomes in CCG-2961, a Children's Oncology Group phase 3 trial for untreated pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 111:1044-1053.

 

Lauring, J., A. M. Abukhdeir, H. Konishi, J. P. Garay, J. P. Gustin, Q. Wang, R. J. Arceci, W. Matsui, and B. H. Park. 2008. The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity. Blood 111:856-64.

 

Meshinchi, S., and R. J. Arceci. 2007. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist 12:341-55.

 

Oliansky, D. M., J. D. Rizzo, P. D. Aplan, R. J. Arceci, L. Leone, Y. Ravindranath, J. E. Sanders, F. O. Smith, 3rd, F. Wilmot, P. L. McCarthy, Jr., and T. Hahn. 2007. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant 13:1-25.

 

Turtzo, L. C., D. D. Lin, H. Hartung, P. B. Barker, R. Arceci, and K. Yohay. 2007. A neurologic presentation of familial hemophagocytic lymphohistiocytosis which mimicked septic emboli to the brain. J Child Neurol 22:863-8.

Williams, K. M., M. A. Higman, A. R. Chen, C. L. Schwartz, M. Wharam, P. Colombani, and R. J. Arceci. 2008. Successful treatment of a child with late onset T-cell post-transplant lymphoproliferative disorder/lymphoma. Pediatr Blood Cancer 50:667-70.

 

Zhang, L., M. S. Anglesio, M. O'Sullivan, F. Zhang, G. Yang, R. Sarao, P. N. Mai, S. Cronin, H. Hara, N. Melnyk, L. Li, T. Wada, P. P. Liu, J. Farrar, R. J. Arceci, P. H. Sorensen, and J. M. Penninger. 2007. The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers. Nat Med 13:1060-9.

 

Arceci, R. J. (2006). Histiocytosis. In:Clinical Hematology (Young, N. S., Gerson, S. L. & High, K. A., eds.), pp. xxvi, 1420 p. Mosby/Elsevier, Philadelphia.

 

Arceci, R. J. (2006). Surviving childhood cancer: a special series on the successes and challenges after "cure". Pediatr Blood Cancer 46, 119-21.

 

Arceci, R. J., Sande, J., Lange, B., Shannon, K., Franklin, J., Hutchinson, R., Vik, T. A., Flowers, D., Aplenc, R., Berger, M. S., Sherman, M. L., Smith, F. O., Bernstein, I. & Sievers, E. L. (2005). Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia. Blood 106, 1183-8.

 

Bechan, G. I., Egeler, R. M. & Arceci, R. J. (2006). Biology of langerhans cells and langerhans cell histiocytosis. Int Rev Cytol 254, 1-43.

 

Becton, D., Dahl, G. V., Ravindranath, Y., Chang, M. N., Behm, F. G., Raimondi, S. C., Head, D. R., Stine, K. C., Lacayo, N. J., Sikic, B. I., Arceci, R. J. & Weinstein, H. (2006). Randomized use of cyclosporin A (CsA) to modulate P-glycoprotein in children with AML in remission: Pediatric Oncology Group Study 9421. Blood 107, 1315-24.

 

Beverley, P. C., Egeler, R. M., Arceci, R. J. & Pritchard, J. (2005). The Nikolas Symposia and histiocytosis. Nat Rev Cancer 5, 488-94.

 

Feldman, A. L., Berthold, F., Arceci, R. J., Abramowsky, C., Shehata, B. M., Mann, K. P., Lauer, S. J., Pritchard, J., Raffeld, M. & Jaffe, E. S. (2005). Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis. Lancet Oncol 6, 435-7.

 

Golub, T. & Arceci, R. J. (2006). Acute myelogenous leukemia. In Principles and Practice of Pediatric Oncology 5th edit. (Pizzo, P. A. & Poplack, D. G., eds.), pp. xiv, 1780 p. Lippincott Williams & Wilkins, Philadelphia.

 

Higman, M. A. & Arceci, R. J. (2005). Leukemias and lymphomas. In Surgery of Infants and Children 2nd edit. (Oldham, K. T., Columbani, P. M., Foglia, R. P. & Skinner, M. A., eds.). Lippincott Williams & Wilkins, Philadelphia, PA.

 

Jeha, S., Gaynon, P. S., Razzouk, B. I., Franklin, J., Kadota, R., Shen, V., Luchtman-Jones, L., Rytting, M., Bomgaars, L. R., Rheingold, S., Ritchey, K., Albano, E., Arceci, R. J., Goldman, S., Griffin, T., Altman, A., Gordon, B., Steinherz, L., Weitman, S. & Steinherz, P. (2006). Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol 24, 1917-23.

 

Kean, L., Arceci, R. J. & Woods, W. G. (2006). Acute myeloid leukemia. In Pediatric Hematology 3rd edit. (Arceci, R., Hann, I. M. & Smith, O. P., eds.), pp. p. Blackwell Publishing, Malden, MA.

 

Kim, G. R., Chen, A. R., Arceci, R. J., Mitchell, S. H., Kokoszka, K. M., Daniel, D. & Lehmann, C. U. (2006). Error reduction in pediatric chemotherapy: computerized order entry and failure modes and effects analysis. Arch Pediatr Adolesc Med 160, 495-8.

 

Meshinchi, S., Arceci, R. J., Sanders, J. E., Smith, F. O., Woods, W. B., Radich, J. P. & Alonzo, T. A. (2006). Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood 108, 400; author reply 400-1.

 

Shahlaee, A. & Arceci, R. J. (2006). Langerhans cell histiocytosis. In Kendig's Disorders of the Respiratory Tract in Children 7th edit. (Chernick, V., Boat, T., Bush, A. & Wilmott, R., eds.), pp. xix, 1111 p. Saunders/Elsevier, Philadelphia, PA.

 

Strouse, J. J., Spevak, M., Mack, A. K., Arceci, R. J., Small, D. & Loeb, D. M. (2005). Significant responses to platinum-based chemotherapy in renal medullary carcinoma. Pediatr Blood Cancer 44, 407-11.

 

Widemann, B. C., Salzer, W. L., Arceci, R. J., Blaney, S. M., Fox, E., End, D., Gillespie, A., Whitcomb, P., Palumbo, J. S., Pitney, A., Jayaprakash, N., Zannikos, P. & Balis, F. M. (2006). Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol 24, 507-16.

 

Arceci, R. J., Sande, J., Lange, B., Shannon, K., Franklin, J., Hutchinson, R., et al. 2005. Safety and efficacy of gemtuzumab ozagamicin (Mylotarg) in pediatric patients with advanced CD33-positive acute myeloid leukemia. Blood. 106:1183-1188.

 

Beverley, P. C. L., Egeler, R. M., Arceci, R. J., & Pritchard, J. 2005. The Nikolas Symposia and histiocytoses. Nat. Rev. Cancer. 5:488-495.

 

Brown, P., Meshinchi, S., Levis, M., Alonzo, T. A., Gerbing, R., Lange, B., et al. 2004. CEP-701, a FLT3 tyrosine kinase inhibitor, is cytotoxic to primary pediatric AML blasts. Blood.

 

Greene, M. E., Mundschau, G., Wechsler, J., McDevitt, M., Gamis, A., Gurbuxani, S., et al. 2003. Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome. Blood Cell. Mol. Dis. 31:351-356.

 

Sun, L. Q., & Arceci, R. J. 2005. Altered epigenetic patterning leading to replicative senescence and reduced longevity: a role of a novel SNF2 factor, PASG. Cell Cycle. 4:3-5.

 

Sun, L. Q., Lee, D. W., Xiao, W., Raabe, E. H., Miao, D., Huso, D. L., et al. 2004. Growth retardation and premature aging in mice with disruption of the SNF2-like gene, PASG. Gene. Dev. 18:1035-1047.