AG LeCoutre

Therapeutic Implications of Oncogenic Tyrosine Kinases in Chronic Myeloproliferative Neoplasias

Forschungsschwerpunkt

In chronic myeloproliferative neoplasias (CMPN) numerous pathogenetically relevant oncoproteins have been identified over the past decades and include among others BCR-ABL1 (chronic myeloid leukemia), JAK2V617F (polycythemia vera, essential thrombocytosis and primary osteomyelofibrosis), mutant MPL515 (essential thrombocytosis), rearrangements of PDGFR (eosinophilia associated CMPNs) and mutant cKIT (systemic mastocytosis). Consequently, the characterization of these oncoproteins led to specific therapeutic approaches.

On a clinical level our research involves the participation in multicentre trials (phase I – III) employing small molecules (imatinib, nilotinib, dasatinib, INNO-406, Bosutinib and INCB18424) as targeted therapies. Here, previous activities adressed the identification of clinical factors of prognostic relevance. Additional ongoing activities include the characterization of specific toxicities of tyrosine kinas inhibitors such as cardiac function or endocriniological adverse events.

On a preclinical level a previous project addressed the frequency of low levels of oncogenic transcripts such as BCR-ABL, PML-RARα or AML1-ETO in healthy individuals as well as in immune suppressed organ transplant recipients.

Ausgewählte Publikationen

Koren-Michowitz M, le Coutre P, Duyster J, Scheid C, Panayiotidis P, Prejzner W, Rowe JM, Schwarz M, Goldschmidt N, Nagler A
Activity and tolerability of nilotinib: a retrospective multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or intolerant.
Cancer 2010;
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM, ENESTnd Investigators
Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia.
N Engl J Med 2010; 362(24):2251-9.
Kantarjian H, le Coutre P, Cortes J, Pinilla-Ibarz J, Nagler A, Hochhaus A, Kimura S, Ottmann O.
Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance.
Cancer 2010; 116(11):2665-72.
Quintàs-Cardama A, Kim TD, Cataldo V, le Coutre P
Nilotinib.
Recent Resuslts Cancer Res 2010; 184:103-17.
Hemmati PG, Terwey TH, Massenkeil G, le Coutre P, Vuong LG, Neuburger S, Dörken B, Arnold R
Reduced intensity conditioning prior to allogeneic stem cell transplantation in first complete remission is effective in patients with acute myeloid leukaemia and an intermediate-risk karyotype .
Int J Hematol 2010; 2010
le Coutre P, Schwarz M, Kim TD
New Developments in Tyrosine Kinase Inhibitor Therapy for Newly Diagnosed Chronic Myeloid Leukemia.
Clin Cancer Res 2010; 16(6):1771-80.
T. D. Kim, S. Türkmen, M. Schwarz, G. Koca, H. Nogai, C. Bommer, B. Dörken, P. Daniel, and P. le Coutre.
Impact of additional chromosomal aberrations and BCR-ABL kinase domain mutations on the response to nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia Haematologica.
Haematologica 2009;
le Coutre P, Reinke P, Neuhaus R, Trappe R, Ringel F, Lalancette M, Hemmati PG, Dörken B, Daniel PT.
BCR-ABL positive cells and chronic myeloid leukaemia in immune suppressed organ transplant recipients..
Eur J Haematol. 2009;
le Coutre P, Meisel H, Hofmann J, Röcken C, Vuong GL, Neuburger S, Hemmati PG, Dörken B, Arnold R.
Reactivation of Indigenous Hepatitis E Infection in a Patient with Acute Lymphoblastic Leukemia after Allogeneic Stem Cell Transplantation..
Gut 2009; 58(5):699-702.
le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, Apperley JF, Larson RA, Abruzzese E, O'Brien SG, Kuliczkowski K, Hochhaus A, Mahon FX, Saglio G, Gobbi M, Kwong YL, Baccarani M, Hughes T, Martinelli G, Radich JP, Zheng M, Shou Y, Kantarjian H.
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated phase chronic myelogenous leukemia..
Blood 2008; 111(4):1834-9.