CURRENT CLINICAL INTERESTS
Acute Myeloid Leukemia
CURRENT RESEARCH INTERESTS
Acute Myeloid Leukemia; CD33; Clinical Trials in AML; Immunotherapy of AML; Leukemia Stem Cells; Predictive Modeling
Our research is focused on human acute myeloid leukemia (AML). We are particularly interested in the delineation of the clonal origin of AML, the molecular and phenotypic characterization of AML stem and progenitor cells, and the interaction between AML cells and their environment. An overarching goal of these laboratory-based studies is the development of targeted treatments aimed to eradicate disease-relevant AML cells, with CD33-directed therapies being one important example for our efforts. We are also involved in the early testing of novel drugs and innovative care approaches in patients with AML. Finally, we participate in collaborative projects utilizing large datasets that aim to improve diagnostic and prognostic tools in AML or, together with epidemiologists, study risk factors for the development of this hematological malignancy.
Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, Linenberger ML. Multidrug resistance protein (MRP) attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood. 2003;102(4):1466-1473.
Walter RB, Raden BW, Cronk MR, Bernstein ID, Appelbaum ID, Banker DE. The peripheral benzodiazepine receptor ligand PK11195 overcomes different resistance mechanisms to sensitize AML cells to gemtuzumab ozogamicin. Blood. 2004;103(11):4276-4284.
Walter RB, Raden BW, Kamikura DM, Cooper JA, Bernstein ID. Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood. 2005:105(3):1295-1302.
Walter RB, Pirga JL, Cronk M, Mayer S, Appelbaum FR, Banker DE. PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism. Blood. 2005;106(10):3584-3593.
Walter RB, Gooley TA, van der Velden VHJ, Loken MR, van Dongen JJM, Flowers DA, Bernstein ID, Appelbaum FR. CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood. 2007;109(10):4168-4170.
Walter RB, Boyle KM, Appelbaum FR, Bernstein ID, Pagel JM. Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts. Blood. 2008;111(9):4813-4816.
Walter RB, Kantarjian HM, Huang X, Pierce SA, Sun Z, Gundacker HM, Ravandi F, Faderl SH, Tallman MS, Appelbaum FR, Estey EH. The effect of complete remission (CR) and CR with incomplete platelet recovery (CRp) on outcome in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group (SWOG), and M.D. Anderson Cancer Center study. J Clin Oncol. 2010;28(10):1766-1771.
Walter RB, Alonzo TA, Gerbing RB, Ho PA, Smith FO, Raimondi SC, Hirsch BA, Gamis AS, Franklin JL, Hurwitz CA, Loken MR, Meshinchi S. High expression of the very late antigen (VLA)-4 integrin independently predicts reduced risk of relapse and improved outcome in pediatric acute myeloid leukemia: a report from the Children’s Oncology Group. J Clin Oncol. 2010;28(17):2831-2838.
Walter RB, Appelbaum FR, Tallman MS, Weiss NS, Larson RA, Estey EH. Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm. Blood.. 2010;116(14):2420-2428.
Walter RB, Gooley TA, Wood BL, Milano F, Fang M, Sorror ML, Estey EH, Salter AI, Lansverk E, Chien JW, Gopal AK, Appelbaum FR, Pagel JM. Impact of pre-transplant minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol. 2011;29(9):1190-1197.
Walter RB, Milano F, Brasky TM, White E. Long-term use of acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs and risk of hematologic malignancies: results from the prospective VITamins and Lifestyle (VITAL) study. J Clin Oncol. 2011;29(17):2424-2431.
Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, Appelbaum FR, Kantarjian HM, Estey EH. Prediction of early death following induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29(33):4417-4424.
Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood. 2012;119(26):6198-6208.
Walter RB, Othus M, Burnett AK, Löwenberg B, Kantarjian HM, Ossenkoppele GJ, Hills RK, van Montfort KGM, Ravandi F, Evans A, Pierce SR, Appelbaum FR, Estey EH. Significance of FAB subclassification of “acute myeloid leukemia, not otherwise specified” in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood. 2013;121(13):2424-2431.