Chief, Division of Leukemia, Department of Medicine
Professor of Medicine, School of Medicine & Biomedical Sciences, University at Buffalo
Assistant Research Professor, Department of Immunology
Immunology Program, Roswell Park Graduate Division

Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo, NY 14263 USA
Tel: 716-845-8447
Fax: 716-845-2343
E-mail: meir.wetzler@roswellpark.org

Dr. Meir Wetzler joined the staff of Roswell Park Cancer Institute (RPCI) in 1994, as Clinician, Division of Leukemia, Department of Medicine. He earned his medical degree from the Hebrew University Hadassah Medical School, Jerusalem, Israel, in 1980, and completed residency training in Internal Medicine at Kaplan Hospital (affiliated with Hebrew University Hadassah Medical School), Rehovot, Israel, in 1986. From 1988 to 1992, he completed fellowships in Clinical Immunology and Biologic Therapy, and in Medical Oncology at M.D. Anderson Cancer Center, Houston, TX.

Dr. Wetzler is licensed in New York, Texas and Israel. He also is Professor of Medicine, School of Medicine & Biomedical Sciences, University of Buffalo, Assistant Research Professor, Immunology Program, Roswell Park Graduate Division, and a member of the Adjunct Faculty, Physician Assistant Department, D’Youville College, Buffalo, NY.

Dr. Wetzler’s research interests focus on the role of signal transducer and activation of transcription in leukemogenesis; the cellular and humoral immune response to leukemic-associated antigens; and cytogenetics in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Dr. Wetzler is a member of the American Society of Clinical Oncology, American Association for Cancer Research, American Society of Hematology, and Israel Medical Association. Currently, he is a member of the Leukemia Core Committee, Cancer and Leukemia Group B, and the Chronic Myeloid Leukemia Treatment Committee, National Comprehensive Cancer Network. He has authored or co-authored more than 100 journal publications, book chapters and abstracts. He serves as Journal Referee for Blood, Cancer, Stem Cells, Leukemia Research, and the American Journal of Hematology.

Description of Research

Dr. Meir Wetzler is a Physician-Scientist with primary interest in leukemia. His research has focused on the involvement of autocrine and paracrine growth factor regulatory loops in the pathogenesis of leukemia.

The current focus of his laboratory is the role of signal transducer and activator of transcription (STAT) proteins in leukemogenesis. Hematopoietic cytokine receptor signaling pathways involve activation of STAT proteins which are postulated to be involved in cellular differentiation. Aberrant STAT isoforms (b forms, rather than the normal a forms) have been described and have been found to block the normal signaling pathway from the receptor.

Dr. Wetzler, in collaboration with Dr. Baumann from the Department of Molecular and Cellular Biology, has recently shown that the b forms were expressed in approximately half of AML samples and that these forms are generated by a proteolytic activity. They propose that the b isoforms of STATs negate the action of the a isoforms and that their expression serves to prevent induction of cytokine-responsive genes, as well as induce or amplify survival signals. Further, constitutive STAT activity was studied as an additional aberration of the signal transduction pathway. Recent work has shown that constitutive STAT3 activity is associated with shorter disease-free survival in AML patients. Dr. Wetzler hypothesizes that the molecular event(s) underlying dysregulated STAT3 activity will be manifested in specific profiles of expressed genes and gene products that participate in the generation of the leukemic phenotype.

Dr. Wetzler also collaborates with Dr. Ferrone from the Department of Immunology on studying immune response to leukemia. It has been demonstrated in animal models that successful generation of specific anti-tumor immune responses can aid in eliminating tumor cells and impede tumor recurrence. As a first step toward achieving this goal, they plan to test the hypothesis that leukemia-associated antigens not present on the surface of the leukemic blasts, will be presented on the surface of dendritic cells generated from these blasts, and that these dendritic cells will be able to mount a specific immune response.

Dr. Wetzler’s interests in leukemia cytogenetics have led him to study the effect of cytogenetic on the outcome of ALL patients enrolled onto the Cancer and Leukemia Group B studies. He has recently shown that the outcome of patients with t(9;22) varies depending on the presence or absence of additional cytogenetic aberrations.

Key Publications

• M. Wetzler, M.T. Brady, E. Tracy, Z.-R. Li, K.A. Donohue, K.L. O'Loughlin, Y. Cheng, A. Mortazavi, A.A. McDonald, P. Kunapuli, P.K. Wallace, M.R. Baer, J.K. Cowell, H. Baumann. Arsenic trioxide affects signal transducer and activator of transcription proteins through alteration of protein tyrosine kinase phosphorylation. Clin Cancer Res 12:6817-6825, 2006
• J.A. Claus, M.T. Brady, J. Lee, K.A. Donohue, S.N. Sait, S. Ferrone, M. Wetzler. T Cell Activation by t(9;22) Acute Lymphoblastic Leukemia-Derived Dendritic-Like Cells is Associated with Increased Tapasin Expression. Cancer Immunology and Immunotherapy 55:160-165, 2006
• M. Wetzler, R.K. Dodge, K. Mrózek, C.C. Stewart, A. Carroll, R.A. Larson, C.D. Bloomfield. The prognostic importance of secondary cytogenetic changes in adult acute lymphoblastic leukemia with t(9;22) – A Cancer and Leukemia Group B study. Br J Haematol, 124:275-288, 2004