CURRENT CLINICAL INTERESTS
and myelodysplastic disorders; acute myeloid leukemia
CURRENT RESEARCH INTERESTS
of leukemic disease progression and therapy resistance, new agents in
the treatment of chronic myeloid leukemia (CML) and acute myeloid
As a physician scientist a translational approach is an overarching theme of my work, with the goal, whenever possible, of finding direct applications to patient care. In my clinical practice I see patients with chronic myeloid leukemia (CML), myeloproliferative neoplasms, and acute myeloid leukemia (AML). My laboratory has generated or analyzed large high-throughput gene and microRNA (miRNA) expression data sets from CML and acute myeloid leukemia AML patient samples to identify genes, miRNAs, and pathways that contribute to leukemogenesis and therapy resistance. We have investigated how specific candidates 1) contribute to disease, 2) can be targeted by existing or new therapeutic strategies and 3) can be used to predict outcomes. Our work has identified gene signatures associated with CML progression to acute leukemia. We have also discovered new roles and direct targets of noncoding RNAs such as miRNAs that contribute to resistance and relapse in AML. The lab is also active in developing tools and assays to better prognosticate outcomes for CML patients. We are also active in the development and clinical trial testing of new therapeutic agents in CML and AML.
Oehler VG, Gooley T, Snyder DS, Johnston L, Lin A, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood. 2007; 109(4): 1782-1789. PMID 17062727.
Oehler VG, Qin J, Ramakrishnan R, Facer G, Ananthnarayan S, et al. Absolute quantitative detection of ABL tyrosine kinase domain point mutations using a novel nanofluidic platform and mutation-specific PCR. Leukemia. 2009; 23(2): 396-399. PMID 18615105.
Oehler VG, Guthrie K, Cummings CL, Sabo K, Wood BL, et al. Preferentially Expressed Antigen in Melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. Blood. 2009;114(15): 3299-3308. PMID 19625708.
Oehler VG*, Yeung KY*, Choi YE, Bumgarner RE, Raftery AE, et al. The derivation of diagnostic markers of chronic myeloid leukemia progression from microarray data. Blood. 2009; 114(15): 3292-3298. PMID 19654405. *Shared first author
Ito H, Kwon HY, Zimdahl B, Congdon KL, Blum J, Lento W, Zhao C, Lagoo A, Gerrard G, Foroni L, Goldman J, Goh H, Kim SH, Kim DW, Chuah C, Oehler VG, Radich J, Jordan CT, and Reya T. Regulation of myeloid leukemia by the cell fate determinant Musashi. Nature. 2010; 466(7307): 765-768. PMID 20639863.
Champagne MA, Fu CH, Chang M, Chen H, Gerbing RB, Alonzo TA, Cooley LD, Heerma NA, Oehler V, et al. Higher dose imatinib for children with de novo chronic phase myelogenous leukemia: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2011; 57(1): 56-62. PMID 21465636.
Yeung KY, Gooley TA, Zhang A, Raftery AE, Radich JP, and Oehler VG. Predicting relapse prior to transplantation in chronic myeloid leukemia by integrating expert knowledge and expression data. Bioinformatics. 2012; 28(6): 823-830.
Cortes JE, Kim DW, Pinella-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. New Engl J Med. 2013; 369(19): 1783-1796 (PACE Investigator).
Morris VA, Zhang A, Yang T, Stirewalt DL, Ramamurthy R, Meshinchi S, and Oehler VG. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells. 2013; PLOS One,8(9): e75815.
Zimdahl B, Ito T, Blevins A, Bajaj J, Konuma T, Weeks J, Koechlein CS, Kwon HY, Arami O, Rizzieri D, Broome HE, Chuah C, Oehler VG, Sasik R, Hardiman G, and Reya T. Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia. Nat Genet. 2014; 46(3): 245-252.
Ostronoff F, Othus M, Lazenby M, Estey E, Appelbaum F, Evans A, Godwin J, Gilkes A, Kopecky KJ, Burnett AK, List AF, Fang M, Oehler V, Petersdorf SH, Pogosova-Agadjanyan E, Radich J, Willman CW, Meshinchi S, and Stirewalt D. Prognostic significance of NPM1 mutations in the absence of FLT3-ITD in older patients with AML: a SWOG and MRC/NCRI report. J Clin Oncol. 2015; 33(10):1157-64.
Kwon HY, Bajaj J, Ito T, Blevins A, Konuma T, Weeks J, Lytle NK, Koechlein CS, Rizzieri D, Chuah C, Oehler VG, Sasik R, Hardiman G, and Reya T. Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia. Cell Stem Cell. 2015; 17(2): 152-164.
Martinelli G, Oehler VG, Papayannnidis C, Courtney R, Shaik, NM, Zhang X, et al. Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study. Lancet Haematology. 2015; 2(8):e339-46.
Morris VA, Cummings C, Korb B, Boaglio SM, and Oehler VG. Deregulated KLF4 expression in myeloid leukemias alters cell proliferation and differentiation through microRNA and gene targets. Mol Cell Biol. 2015 ; 36(4): 559. PMCID: PMC4751692.
Soma L, Oehler VG, Ding C, and Cherian S. Small, abnormal B lymphoid blast populations in Chronic Myelogenous Leukemia at diagnosis: Does this finding indicate an accelerated course? Cytometry B Clin Cytom. 2016; published online January 21, 2016 as doi: 10.1002/cyto.b.21357.
Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, Etienne G, Nicolini FE, Le Coutre P, Clark R, Stenke L, Andorsky D, Oehler V, Lustgarten S, Rivera VM, Clackson T, Haluska FG, Baccarani M, Cortes JE, Guilhot F, Hochhaus A, Hughes T, Kantarjian HM, Shah NP, Talpaz M, Deininger MW for the EPIC Investigators. Ponatinib Versus Imatinib in Newly Diagnosed Chronic Myeloid Leukemia: an International, Randomized, Open-Label, Phase 3 Trial. Lancet Oncology. 2016; 17(5): 612-621.
Brehme M, Koschmieder S, Montazeri M, Copland M, Oehler VG, Radich JP, Brummendorf TH, and Schuppert A. Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia. Sci Rep. 2016; published online April 6, 2016 as doi: 10.1038/srep24057.
Ramamurthy R, Hughes M, Morris V, Bolouri H, Gerbing RB, Wang YC, Loken MR, Raimondi SC, Hirsch BA, Gamis AS, Oehler VG, Alonzo TA, and Meshinchi S. miR-155 expression and correlation with clinical outcome in pediatric AML: A report from Children's Oncology Group. Pediatr Blood Cancer. 2016; published on line August 11, 2016 as doi: 10.1002/pbc.26157.
Son HN, Srinivasan S, Yhee JY, Das D, Daugherty BK, Berguig GY, Oehler VG, Kim SH, Kim K, Kwon IC, Stayton PS, and Convertine AJ. Chemotherapeutic copolymers prepared via the RAFT polymerization of prodrug monomers. Polymer chemistry. 2016; 7 (27): 4494-4505.
Bajaj J, Konuma T, Lytle NK, Kwon HY, Ablack JN, Cantor JM, Rizzieri D, Chuah C, Oehler VG, Broome EH, Ball ED, van der Horst EH, Ginsberg MH, and Reya, T. CD98-mediated adhesive signaling enables the establishment and propagation of acute myelogenous leukemia. Cancer Cell. Published online November 14, 2016 as doi.org/10.1016/j.ccell.2016.10.003.