![Martin Ruthardt](https://profiles-cardiff.imgix.net/attachments/2592?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Martin Ruthardt
Senior Lecturer in Haematology, Division of Cancer and Genetics
Publication
2023
- Sternsdorf, T., Puccetti, E., Jensen, K., Hoelzer, D., Will, H., Ottmann, O. G. and Ruthardt, M. 2023. PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.. Molecular and Cellular Biology 19(7), pp. 5170-5178. (10.1128/mcb.19.7.5170)
- Müller-Tidow, C. et al. 2023. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells.. Molecular and Cellular Biology 24(7), pp. 2890-2904. (10.1128/MCB.24.7.2890-2904.2004)
2022
- Chiriches, C. et al. 2022. Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia. Annals of Hematology 101, pp. 2179-2193. (10.1007/s00277-022-04905-9)
- Chiriches, C. et al. 2022. Understanding a high-risk acute myeloid leukemia by analyzing the interactome of its major driver mutation. PLoS Genetics 18(10), article number: e1010463. (10.1371/journal.pgen.1010463)
2021
- Mian, A. A. et al. 2021. Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR/ABL1 and its resistance and compound mutants BCR/ABL1T315I and BCR/ABL1T315I-E255K. Annals of Hematology 100, pp. 2023-2029. (10.1007/s00277-020-04357-z)
- Regev, O., Kidan, N., Nicola, M., Khamisie, H., Ruthardt, M. and Mahajna, J. 2021. Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells. Archives of Medical Science 17(1), pp. 266–274. (10.5114/aoms.2020.101042)
2020
- Oancea, C., Rüster, B., Henschler, R., Puccetti, E. and Ruthardt, M. 2020. The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation.. Leukemia 24, pp. 1910–1919. (10.1038/leu.2010.180)
2019
- Mian, A. A. et al. 2019. The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis. Leukemia 33, pp. 2319-2323. (10.1038/s41375-019-0468-y)
2017
- Kidan, N. et al. 2017. Ectopic expression of snail and twist in Ph+ leukemia cells upregulates CD44 expression and alters their differentiation potential. Journal of Cancer 8(19), pp. 3952-3968. (10.7150/jca.19633)
2016
- Ratzon, E., Najajreh, Y., Salem, R., Khamaisie, H., Ruthardt, M. and Mahajna, J. 2016. Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study. BMC Cancer 16, article number: 140. (10.1186/s12885-016-2182-8)
- Haberbosch, I., Rafiei, A., Oancea, C., Ottmann, O., Ruthardt, M. and Mian, A. 2016. BCR: a new target in resistance mediated by BCR/ABL-315I?. Genes & Cancer 7(1-2), pp. 36-46.
2015
- Mian, A. A. et al. 2015. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia 29(5), pp. 1104-1114. (10.1038/leu.2014.326)
- Rafiei, A. et al. 2015. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive Acute Lymphatic Leukemia. PLOS Genetics 11(4), article number: e1005144. (10.1371/journal.pgen.1005144)
- Mian, A. A. et al. 2015. Potential use of allosteric inhibitors as strategy to overcome drug resistance in Ph-positive leukemia. International Journal of Molecular Medicine 36, pp. S26-S26.
2014
- Mian, A., Rafiei, A., Oancea, C., Ottmann, O. and Ruthardt, M. 2014. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome positive Acute Lymphatic Leukemia. Blood 124(21), article number: 2402.
- Oancea, C. et al. 2014. STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML.. Genes & Cancer 5(11-12), pp. 378-392. (10.18632/genesandcancer.39)
- Roos, J. et al. 2014. 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia. Cancer Research 74(18), pp. 5244-5255. (10.1158/0008-5472.CAN-13-3012)
2013
- Badura, S. et al. 2013. Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia.. PLOS ONE 8(11), article number: e80070. (10.1371/journal.pone.0080070)
- Najajreh, Y., Khamaisie, H., Ruimi, N., Khatib, S., Katzhendler, J., Ruthardt, M. and Mahajna, J. 2013. Oleylamine-carbonyl-valinol inhibits auto-phosphorylation activity of native and T315I mutated Bcr-Abl, and exhibits selectivity towards oncogenic Bcr-Abl in SupB15 ALL cell lines.. Molecular Biology Reports 40, pp. 2205–2213. (10.1007/s11033-012-2282-8)
2012
- Khateb, M. et al. 2012. Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism.. BMC Cancer 12, article number: 563. (10.1186/1471-2407-12-563)
- Mian, A. A. et al. 2012. Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I.. BMC Cancer 12(411) (10.1186/1471-2407-12-411)
- Romanski, A. et al. 2012. Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells.. Cell Cycle 11(17), pp. 3219-3226. (10.4161/cc.21565)
- Mian, A. A., Metodieva, A., Najajreh, Y., Ottmann, O. G., Mahajna, J. and Ruthardt, M. 2012. p185(BCR/ABL) has a lower sensitivity than p210(BCR/ABL) to the allosteric inhibitor GNF-2 in Philadelphia chromosome-positive acute lymphatic leukemia.. Haematologica 97(2) (10.3324/haematol.2011.047191)
- Rettinger, E. et al. 2012. The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.. Cytotherapy 14(1), pp. 91-103. (10.3109/14653249.2011.613931)
2011
- Steinert, G., Oancea, C., Roos, J., Hagemeyer, H., Maier, T., Ruthardt, M. and Puccetti, E. 2011. Sulindac sulfide reverses aberrant self-renewal of progenitor cells induced by the AML-associated fusion proteins PML/RARα and PLZF/RARα.. PLoS ONE 6(7), article number: e22540. (10.1371/journal.pone.0022540)
- Khamaisie, H., Sussan, S., Tal, M., Najajreh, Y., Ruthardt, M. and Mahajna, J. 2011. Oleic acid is the active component in the mushroom Daedalea gibbosa inhibiting Bcr-Abl kinase autophosphorylation activity.. Anticancer Research 31(1), pp. 177-183.
2010
- Steinhilber, D., Fischer, A. S., Metzner, J., Steinbrink, S. D., Roos, J., Ruthardt, M. and Maier, T. J. 2010. 5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.. Frontiers in Pharmacology 1(143) (10.3389/fphar.2010.00143)
- Bursen, A., Schwabe, K., Rüster, B., Henschler, R., Ruthardt, M., Dingermann, T. and Marschalek, R. 2010. The AF4·MLL fusion protein is capable of inducing ALL in mice without requirement of MLL·AF4. Blood 115(17), pp. 3570–3579. (10.1182/blood-2009-06-229542)
2009
- Mian, A. A., Oancea, C., Zhao, Z., Ottmann, O. G. and Ruthardt, M. 2009. Oligomerization inhibition, combined with allosteric inhibition, abrogates the transformation potential of T315I-positive BCR/ABL. Leukemia 23, pp. 2242–2247. (10.1038/leu.2009.194)
- Zheng, X., Oancea, C., Henschler, R., Moore, M. A. S. and Ruthardt, M. 2009. Reciprocal t(9;22) ABL/BCR fusion proteins: Leukemogenic potential and effects on B cell commitment. PLoS ONE 4(10), article number: e7661. (10.1371/journal.pone.0007661)
- Mian, A. A. et al. 2009. The gatekeeper mutation T315I confers resistance against small molecules by increasing or restoring the ABL-kinase activity accompanied by aberrant transphosphorylation of endogenous BCR, even in loss-of-function mutants of BCR/ABL.. Leukemia 23, pp. 1614–1621. (10.1038/leu.2009.69)
- Boehrer, S., Chow, K. U., Ruthardt, M., Hoelzer, D., Mitrou, P. S. and Weidmann, E. 2009. Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells.. Leukemia & Lymphoma 43(9), pp. 1737-1741. (10.1080/1042819021000006510)
- Zheng, X., Oancea, C., Henschler, R. and Ruthardt, M. 2009. Cooperation between constitutively activated c-kit signaling and leukemogenic transcription factors in the determination of the leukemic phenotype in murine hematopoietic stem cells.. International Journal of Oncology 34(6), pp. 1521-1531. (10.3892/ijo_00000281)
- Gwanmesia, P. M., Romanski, A., Schwarz, K., Bacic, B., Ruthardt, M. and Ottmann, O. G. 2009. The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines.. BMC Cancer 9, article number: 53. (10.1186/1471-2407-9-53)
2008
- Beissert, T., Hundertmark, A., Kaburova, V., Travaglini, L., Mian, A. A., Nervi, C. and Ruthardt, M. 2008. Targeting of the N-terminal coiled coil oligomerization interface by a helix-2 peptide inhibits unmutated and imatinib-resistant BCR/ABL. International Journal of Cancer 122(12), pp. 2744-2752. (10.1002/ijc.23467)
2007
- Bug, G. et al. 2007. Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia.. Haematologica 92(4) (10.3324/haematol.10758)
- Zheng, X. et al. 2007. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells.. Haematologica 92(3) (10.3324/haematol.10541)
- Yokota, A. et al. 2007. INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity. Blood 109(1), pp. 306–314. (10.1182/blood-2006-03-013250)
2006
- Zheng, X., Güller, S., Beissert, T., Puccetti, E. and Ruthardt, M. 2006. BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility.. BMC Cancer 6, article number: 262. (10.1186/1471-2407-6-262)
- Boehrer, S. et al. 2006. Prostate-apoptosis-response-gene-4 increases sensitivity to TRAIL-induced apoptosis.. Leukemia Research 30(5), pp. 597-605. (10.1016/j.leukres.2005.09.003)
2005
- Bug, G. et al. 2005. Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia. Cancer 104(12), pp. 2717-2725. (10.1002/cncr.21589)
- Puccetti, E. et al. 2005. The integrity of the charged pocket in the BTB/POZ domain is essential for the phenotype induced by the leukemia-associated t(11;17) fusion protein PLZF/RARalpha.. Cancer Research 65(14), pp. 6080–6088. (10.1158/0008-5472.CAN-04-3631)
- Pramanik, K., Trüpschuch, S., Greiner, A., Ruthardt, M., Henschler, R. and Müller, A. M. 2005. The aorta-gonad-mesonephros-derived stroma cell line DAS104-4 induces differentiation of leukemic cells. Leukemia Research 32(5), pp. 781-789. (10.1016/j.leukres.2007.09.014)
- Bug, G. et al. 2005. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells.. Cancer Research 65(7), pp. 2537–2541. (10.1158/0008-5472.CAN-04-3011)
2004
- Boehrer, S. et al. 2004. In the erythroleukemic cell line HEL Prostate-apoptosis-response-gene-4 (par-4) fails to down-regulate Bcl-2 and to promote apoptosis.. Leukemia & Lymphoma 45(7), pp. 1445-1451. (10.1080/10428190410001663617)
- Kukoc-Zivojnov, N. et al. 2004. Prostate apoptosis response gene-4 (par-4) abrogates the survival function of p185(BCR-ABL) in hematopoietic cells. Experimental Hematology 32(7), pp. 649-656. (10.1016/j.exphem.2004.04.004)
- Puccetti, E. and Ruthardt, M. 2004. Acute promyelocytic leukemia: PML/RARalpha and the leukemic stem cell.. Leukemia 18, pp. 1169–1175. (10.1038/sj.leu.2403367)
- Brieger, A. et al. 2004. In bcr-abl-positive myeloid cells resistant to conventional chemotherapeutic agents, expression of Par-4 increases sensitivity to imatinib (STI571) and histone deacetylase-inhibitors.. Biochemical Pharmacology 68(1), pp. 85-93. (10.1016/j.bcp.2004.02.028)
- Zheng, X. et al. 2004. Gamma-catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells.. Blood 103(9), pp. 3535–3543. (10.1182/blood-2003-09-3335)
- Zang, C. et al. 2004. Peroxisome proliferator-activated receptor gamma ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia.. Leukemia Research 28(4), pp. 387-397. (10.1016/j.leukres.2003.07.005)
- Romanski, A. et al. 2004. Use of a novel histone deacetylase inhibitor to induce apoptosis in cell lines of acute lymphoblastic leukemia.. Haematologica 89(4), pp. 419-426.
2003
- Beissert, T. et al. 2003. Targeting of the N-terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR-ABL and increases sensitivity to STI571.. Blood 102(8), pp. 2985–2993. (10.1182/blood-2003-03-0811)
- Puccetti, E., Beissert, T., Güller, S., Li, J. E., Hoelzer, D., Ottmann, O. G. and Ruthardt, M. 2003. Leukemia-associated translocation products able to activate RAS modify PML and render cells sensitive to arsenic-induced apoptosis.. Oncogene 22, pp. 6900–6908. (10.1038/sj.onc.1206747)
- Chow, K. U. et al. 2003. Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation.. Biochemical Pharmacology 66(5), pp. 711-724. (10.1016/S0006-2952(03)00410-6)
2002
- Puccetti, E. et al. 2002. AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor.. Cancer Research 62(23), pp. 7050–7058.
- Möller, B. et al. 2002. Folinic acid antagonizes methotrexate-induced differentiation of monocyte progenitors.. Rheumatology International 22, pp. 60–67. (10.1007/s00296-002-0188-9)
- Maurer, A. B. et al. 2002. The Stat5-RARalpha fusion protein represses transcription and differentiation through interaction with a corepressor complex.. Blood 99(8), pp. 2647–2652. (10.1182/blood.V99.8.2647)
- Boehrer, S. et al. 2002. In lymphatic cells par-4 sensitizes to apoptosis by down-regulating bcl-2 and promoting disruption of mitochondrial membrane potential and caspase activation.. Cancer Research 62(6), pp. 1768–1775.
2000
- Puccetti, E., Güller, S., Orleth, A., Brüggenolte, N., Hoelzer, D., Ottmann, O. G. and Ruthardt, M. 2000. BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. Cancer Research 60(13), pp. 3409–3413.
1998
- Nervi, C. et al. 1998. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein.. Blood 92(7), pp. 2244-2251. (10.1182/blood.V92.7.2244)
- Ruthardt, M. et al. 1998. The acute promyelocytic leukaemia specific PML and PLZF proteins localize to adjacent and functionally distinct nuclear bodies.. Oncogene 16, pp. 1945–1953. (10.1038/sj.onc.1201722)
- He, L., Guidez, F., Tribioli, C., Peruzzi, D., Ruthardt, M., Zelent, A. and Pandolfi, P. P. 1998. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL.. Nature Genetics 18, pp. 126–135. (10.1038/ng0298-126)
1997
- Ruthardt, M. et al. 1997. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.. Molecular and Cellular Biology 17(8), pp. 4859-4869. (10.1128/MCB.17.8.4859)
- Benedetti, L. et al. 1997. Characterization of the retinoid binding properties of the major fusion products present in acute promyelocytic leukemia cells.. Blood 90(3), pp. 1175-1185. (10.1182/blood.V90.3.1175)
1995
- Avantaggiato, V., Pandolfi, P., Ruthardt, M., Hawe, N., Acampora, D., Pelicci, P. and Simeone, A. 1995. Developmental analysis of murine Promyelocyte Leukemia Zinc Finger (PLZF) gene expression: implications for the neuromeric model of the forebrain organization.. Journal of Neuroscience 15(7), pp. 4927-4942. (10.1523/JNEUROSCI.15-07-04927.1995)
Articles
- Sternsdorf, T., Puccetti, E., Jensen, K., Hoelzer, D., Will, H., Ottmann, O. G. and Ruthardt, M. 2023. PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia.. Molecular and Cellular Biology 19(7), pp. 5170-5178. (10.1128/mcb.19.7.5170)
- Müller-Tidow, C. et al. 2023. Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells.. Molecular and Cellular Biology 24(7), pp. 2890-2904. (10.1128/MCB.24.7.2890-2904.2004)
- Chiriches, C. et al. 2022. Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia. Annals of Hematology 101, pp. 2179-2193. (10.1007/s00277-022-04905-9)
- Chiriches, C. et al. 2022. Understanding a high-risk acute myeloid leukemia by analyzing the interactome of its major driver mutation. PLoS Genetics 18(10), article number: e1010463. (10.1371/journal.pgen.1010463)
- Mian, A. A. et al. 2021. Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR/ABL1 and its resistance and compound mutants BCR/ABL1T315I and BCR/ABL1T315I-E255K. Annals of Hematology 100, pp. 2023-2029. (10.1007/s00277-020-04357-z)
- Regev, O., Kidan, N., Nicola, M., Khamisie, H., Ruthardt, M. and Mahajna, J. 2021. Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells. Archives of Medical Science 17(1), pp. 266–274. (10.5114/aoms.2020.101042)
- Oancea, C., Rüster, B., Henschler, R., Puccetti, E. and Ruthardt, M. 2020. The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation.. Leukemia 24, pp. 1910–1919. (10.1038/leu.2010.180)
- Mian, A. A. et al. 2019. The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis. Leukemia 33, pp. 2319-2323. (10.1038/s41375-019-0468-y)
- Kidan, N. et al. 2017. Ectopic expression of snail and twist in Ph+ leukemia cells upregulates CD44 expression and alters their differentiation potential. Journal of Cancer 8(19), pp. 3952-3968. (10.7150/jca.19633)
- Ratzon, E., Najajreh, Y., Salem, R., Khamaisie, H., Ruthardt, M. and Mahajna, J. 2016. Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study. BMC Cancer 16, article number: 140. (10.1186/s12885-016-2182-8)
- Haberbosch, I., Rafiei, A., Oancea, C., Ottmann, O., Ruthardt, M. and Mian, A. 2016. BCR: a new target in resistance mediated by BCR/ABL-315I?. Genes & Cancer 7(1-2), pp. 36-46.
- Mian, A. A. et al. 2015. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia 29(5), pp. 1104-1114. (10.1038/leu.2014.326)
- Rafiei, A. et al. 2015. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive Acute Lymphatic Leukemia. PLOS Genetics 11(4), article number: e1005144. (10.1371/journal.pgen.1005144)
- Mian, A. A. et al. 2015. Potential use of allosteric inhibitors as strategy to overcome drug resistance in Ph-positive leukemia. International Journal of Molecular Medicine 36, pp. S26-S26.
- Mian, A., Rafiei, A., Oancea, C., Ottmann, O. and Ruthardt, M. 2014. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome positive Acute Lymphatic Leukemia. Blood 124(21), article number: 2402.
- Oancea, C. et al. 2014. STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML.. Genes & Cancer 5(11-12), pp. 378-392. (10.18632/genesandcancer.39)
- Roos, J. et al. 2014. 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia. Cancer Research 74(18), pp. 5244-5255. (10.1158/0008-5472.CAN-13-3012)
- Badura, S. et al. 2013. Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia.. PLOS ONE 8(11), article number: e80070. (10.1371/journal.pone.0080070)
- Najajreh, Y., Khamaisie, H., Ruimi, N., Khatib, S., Katzhendler, J., Ruthardt, M. and Mahajna, J. 2013. Oleylamine-carbonyl-valinol inhibits auto-phosphorylation activity of native and T315I mutated Bcr-Abl, and exhibits selectivity towards oncogenic Bcr-Abl in SupB15 ALL cell lines.. Molecular Biology Reports 40, pp. 2205–2213. (10.1007/s11033-012-2282-8)
- Khateb, M. et al. 2012. Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism.. BMC Cancer 12, article number: 563. (10.1186/1471-2407-12-563)
- Mian, A. A. et al. 2012. Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I.. BMC Cancer 12(411) (10.1186/1471-2407-12-411)
- Romanski, A. et al. 2012. Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells.. Cell Cycle 11(17), pp. 3219-3226. (10.4161/cc.21565)
- Mian, A. A., Metodieva, A., Najajreh, Y., Ottmann, O. G., Mahajna, J. and Ruthardt, M. 2012. p185(BCR/ABL) has a lower sensitivity than p210(BCR/ABL) to the allosteric inhibitor GNF-2 in Philadelphia chromosome-positive acute lymphatic leukemia.. Haematologica 97(2) (10.3324/haematol.2011.047191)
- Rettinger, E. et al. 2012. The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.. Cytotherapy 14(1), pp. 91-103. (10.3109/14653249.2011.613931)
- Steinert, G., Oancea, C., Roos, J., Hagemeyer, H., Maier, T., Ruthardt, M. and Puccetti, E. 2011. Sulindac sulfide reverses aberrant self-renewal of progenitor cells induced by the AML-associated fusion proteins PML/RARα and PLZF/RARα.. PLoS ONE 6(7), article number: e22540. (10.1371/journal.pone.0022540)
- Khamaisie, H., Sussan, S., Tal, M., Najajreh, Y., Ruthardt, M. and Mahajna, J. 2011. Oleic acid is the active component in the mushroom Daedalea gibbosa inhibiting Bcr-Abl kinase autophosphorylation activity.. Anticancer Research 31(1), pp. 177-183.
- Steinhilber, D., Fischer, A. S., Metzner, J., Steinbrink, S. D., Roos, J., Ruthardt, M. and Maier, T. J. 2010. 5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.. Frontiers in Pharmacology 1(143) (10.3389/fphar.2010.00143)
- Bursen, A., Schwabe, K., Rüster, B., Henschler, R., Ruthardt, M., Dingermann, T. and Marschalek, R. 2010. The AF4·MLL fusion protein is capable of inducing ALL in mice without requirement of MLL·AF4. Blood 115(17), pp. 3570–3579. (10.1182/blood-2009-06-229542)
- Mian, A. A., Oancea, C., Zhao, Z., Ottmann, O. G. and Ruthardt, M. 2009. Oligomerization inhibition, combined with allosteric inhibition, abrogates the transformation potential of T315I-positive BCR/ABL. Leukemia 23, pp. 2242–2247. (10.1038/leu.2009.194)
- Zheng, X., Oancea, C., Henschler, R., Moore, M. A. S. and Ruthardt, M. 2009. Reciprocal t(9;22) ABL/BCR fusion proteins: Leukemogenic potential and effects on B cell commitment. PLoS ONE 4(10), article number: e7661. (10.1371/journal.pone.0007661)
- Mian, A. A. et al. 2009. The gatekeeper mutation T315I confers resistance against small molecules by increasing or restoring the ABL-kinase activity accompanied by aberrant transphosphorylation of endogenous BCR, even in loss-of-function mutants of BCR/ABL.. Leukemia 23, pp. 1614–1621. (10.1038/leu.2009.69)
- Boehrer, S., Chow, K. U., Ruthardt, M., Hoelzer, D., Mitrou, P. S. and Weidmann, E. 2009. Expression and function of prostate-apoptosis-response-gene-4 in lymphatic cells.. Leukemia & Lymphoma 43(9), pp. 1737-1741. (10.1080/1042819021000006510)
- Zheng, X., Oancea, C., Henschler, R. and Ruthardt, M. 2009. Cooperation between constitutively activated c-kit signaling and leukemogenic transcription factors in the determination of the leukemic phenotype in murine hematopoietic stem cells.. International Journal of Oncology 34(6), pp. 1521-1531. (10.3892/ijo_00000281)
- Gwanmesia, P. M., Romanski, A., Schwarz, K., Bacic, B., Ruthardt, M. and Ottmann, O. G. 2009. The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines.. BMC Cancer 9, article number: 53. (10.1186/1471-2407-9-53)
- Beissert, T., Hundertmark, A., Kaburova, V., Travaglini, L., Mian, A. A., Nervi, C. and Ruthardt, M. 2008. Targeting of the N-terminal coiled coil oligomerization interface by a helix-2 peptide inhibits unmutated and imatinib-resistant BCR/ABL. International Journal of Cancer 122(12), pp. 2744-2752. (10.1002/ijc.23467)
- Bug, G. et al. 2007. Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia.. Haematologica 92(4) (10.3324/haematol.10758)
- Zheng, X. et al. 2007. Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells.. Haematologica 92(3) (10.3324/haematol.10541)
- Yokota, A. et al. 2007. INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity. Blood 109(1), pp. 306–314. (10.1182/blood-2006-03-013250)
- Zheng, X., Güller, S., Beissert, T., Puccetti, E. and Ruthardt, M. 2006. BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility.. BMC Cancer 6, article number: 262. (10.1186/1471-2407-6-262)
- Boehrer, S. et al. 2006. Prostate-apoptosis-response-gene-4 increases sensitivity to TRAIL-induced apoptosis.. Leukemia Research 30(5), pp. 597-605. (10.1016/j.leukres.2005.09.003)
- Bug, G. et al. 2005. Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia. Cancer 104(12), pp. 2717-2725. (10.1002/cncr.21589)
- Puccetti, E. et al. 2005. The integrity of the charged pocket in the BTB/POZ domain is essential for the phenotype induced by the leukemia-associated t(11;17) fusion protein PLZF/RARalpha.. Cancer Research 65(14), pp. 6080–6088. (10.1158/0008-5472.CAN-04-3631)
- Pramanik, K., Trüpschuch, S., Greiner, A., Ruthardt, M., Henschler, R. and Müller, A. M. 2005. The aorta-gonad-mesonephros-derived stroma cell line DAS104-4 induces differentiation of leukemic cells. Leukemia Research 32(5), pp. 781-789. (10.1016/j.leukres.2007.09.014)
- Bug, G. et al. 2005. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells.. Cancer Research 65(7), pp. 2537–2541. (10.1158/0008-5472.CAN-04-3011)
- Boehrer, S. et al. 2004. In the erythroleukemic cell line HEL Prostate-apoptosis-response-gene-4 (par-4) fails to down-regulate Bcl-2 and to promote apoptosis.. Leukemia & Lymphoma 45(7), pp. 1445-1451. (10.1080/10428190410001663617)
- Kukoc-Zivojnov, N. et al. 2004. Prostate apoptosis response gene-4 (par-4) abrogates the survival function of p185(BCR-ABL) in hematopoietic cells. Experimental Hematology 32(7), pp. 649-656. (10.1016/j.exphem.2004.04.004)
- Puccetti, E. and Ruthardt, M. 2004. Acute promyelocytic leukemia: PML/RARalpha and the leukemic stem cell.. Leukemia 18, pp. 1169–1175. (10.1038/sj.leu.2403367)
- Brieger, A. et al. 2004. In bcr-abl-positive myeloid cells resistant to conventional chemotherapeutic agents, expression of Par-4 increases sensitivity to imatinib (STI571) and histone deacetylase-inhibitors.. Biochemical Pharmacology 68(1), pp. 85-93. (10.1016/j.bcp.2004.02.028)
- Zheng, X. et al. 2004. Gamma-catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells.. Blood 103(9), pp. 3535–3543. (10.1182/blood-2003-09-3335)
- Zang, C. et al. 2004. Peroxisome proliferator-activated receptor gamma ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia.. Leukemia Research 28(4), pp. 387-397. (10.1016/j.leukres.2003.07.005)
- Romanski, A. et al. 2004. Use of a novel histone deacetylase inhibitor to induce apoptosis in cell lines of acute lymphoblastic leukemia.. Haematologica 89(4), pp. 419-426.
- Beissert, T. et al. 2003. Targeting of the N-terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR-ABL and increases sensitivity to STI571.. Blood 102(8), pp. 2985–2993. (10.1182/blood-2003-03-0811)
- Puccetti, E., Beissert, T., Güller, S., Li, J. E., Hoelzer, D., Ottmann, O. G. and Ruthardt, M. 2003. Leukemia-associated translocation products able to activate RAS modify PML and render cells sensitive to arsenic-induced apoptosis.. Oncogene 22, pp. 6900–6908. (10.1038/sj.onc.1206747)
- Chow, K. U. et al. 2003. Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation.. Biochemical Pharmacology 66(5), pp. 711-724. (10.1016/S0006-2952(03)00410-6)
- Puccetti, E. et al. 2002. AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor.. Cancer Research 62(23), pp. 7050–7058.
- Möller, B. et al. 2002. Folinic acid antagonizes methotrexate-induced differentiation of monocyte progenitors.. Rheumatology International 22, pp. 60–67. (10.1007/s00296-002-0188-9)
- Maurer, A. B. et al. 2002. The Stat5-RARalpha fusion protein represses transcription and differentiation through interaction with a corepressor complex.. Blood 99(8), pp. 2647–2652. (10.1182/blood.V99.8.2647)
- Boehrer, S. et al. 2002. In lymphatic cells par-4 sensitizes to apoptosis by down-regulating bcl-2 and promoting disruption of mitochondrial membrane potential and caspase activation.. Cancer Research 62(6), pp. 1768–1775.
- Puccetti, E., Güller, S., Orleth, A., Brüggenolte, N., Hoelzer, D., Ottmann, O. G. and Ruthardt, M. 2000. BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. Cancer Research 60(13), pp. 3409–3413.
- Nervi, C. et al. 1998. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein.. Blood 92(7), pp. 2244-2251. (10.1182/blood.V92.7.2244)
- Ruthardt, M. et al. 1998. The acute promyelocytic leukaemia specific PML and PLZF proteins localize to adjacent and functionally distinct nuclear bodies.. Oncogene 16, pp. 1945–1953. (10.1038/sj.onc.1201722)
- He, L., Guidez, F., Tribioli, C., Peruzzi, D., Ruthardt, M., Zelent, A. and Pandolfi, P. P. 1998. Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL.. Nature Genetics 18, pp. 126–135. (10.1038/ng0298-126)
- Ruthardt, M. et al. 1997. Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling.. Molecular and Cellular Biology 17(8), pp. 4859-4869. (10.1128/MCB.17.8.4859)
- Benedetti, L. et al. 1997. Characterization of the retinoid binding properties of the major fusion products present in acute promyelocytic leukemia cells.. Blood 90(3), pp. 1175-1185. (10.1182/blood.V90.3.1175)
- Avantaggiato, V., Pandolfi, P., Ruthardt, M., Hawe, N., Acampora, D., Pelicci, P. and Simeone, A. 1995. Developmental analysis of murine Promyelocyte Leukemia Zinc Finger (PLZF) gene expression: implications for the neuromeric model of the forebrain organization.. Journal of Neuroscience 15(7), pp. 4927-4942. (10.1523/JNEUROSCI.15-07-04927.1995)
Research
My collaborators and Ihave an interdisciplinary approach on mechanisms of leukemogenesis with a focus on high risk acute leukemia. Our aim is to understand resistance mechanisms and how to hit the weak points of these leukemias for an improvement of already existing therapy concepts. This is always accompanied by the development of novel hypothesis driven molecular therapy approaches. The final goal of all this is to substitute therapy schemes e.g. in acute myeloid leukemia that are in place nearly unchanged for the last thirty years and only profited from improved care and the advances of heterologeous stem cell transplantation.
Interdisciplinary for us is not only a buzz word but something that we believe to be indispensable to achieve our aims Therefore we are able to integrate leukemia stem cell biology with drug development, all types of proteomic approaches, high profile bioinformatics, and clinical risk stratification based on big next generation sequencing data sets.
My collaborators and I contributed successfully to
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understanding all trans retinoic acid (ATRA) response/resistance in acute promyelocytic leukemia (APL/AML-M3).
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understanding of leukemic stem cells as targets of Arsen Trioxyde (ATO) in APL and thereby of the mechanisms on that the novel "chemotherapy free" approach to treat APL by ATRA/ATO is based on.
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determining the importance of leukemic stem cells for the initiation and maintenance of AML and the role of key factors of the WNT-signaling pathway in leukemic stem cells.
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disclosing the contribution of reciprocal translocation products such as ABL-BCR in the t(9;22) to the induction and maintenance of acute and chronic leukemia.
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establishing novel compounds (e.g. PF114) for the treatment of resistant acute and chronic leukemia.
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determining the target cell of t(6;9)DEK-NUP214 mediated transformation and thus the cells to be hit in order to eradicate this high risk acute leukemia.
My collaborators and I are developing our research further by integrating genomics and proteomics (e.g. phospho-proteomics, interactomics) and the bioinformatics needed for a correct elaboration of these big data sets in the solution of our scientific questions.
In addition, we elaborate NSG data sets from big AML and MDS patient cohorts (targeted sequencing, whole exome sequencing and whole genome sequencing) by different algorithms to answer questions about risk stratification, therapy response, and pathogenetic mechanisms. Final aim is to expand the application of these algorithms to other subtypes of cancer.
Biography
Instruction
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1975 - 1984 |
Baccalaureate (humanistic/scientific), Humboldt-Gymnasium, Ulm, Germany |
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1985 - 1993 |
Graduation in Medicine, Università degli Studi, Perugia, Italy |
Research and Professional Experiences
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1990 |
Stage in the Institute of Biochemistry, Medical School of the University Strasbourg, France: "Characterization of the DNA-binding domain of ETS (P. Chambon, B. Wasylyk). |
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1991 – 1993 |
MD thesis: "Acute promyelocytic leukaemia: evaluation of the response to therapy by RT-PCR" in the Laboratory of Molecular Biology (P.G. Pelicci), Università di Perugia, Italy |
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1993 – 1996 |
Postdoctoral in the Laboratory of Molecular Biology (P.G. Pelicci) at the Institute of Oncological Sciences, Università di Perugia, Italy |
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1996 - 2001 |
Group Leader "The molecular biology of leukemogenesis", Department of Hematology, Medical School of the Goethe University, Frankfurt, GermanyV-MR |
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2002-2015 |
Head of the Laboratory of Tumor Stem Cell Biology, Department of Hematology, University Medical School, Frankfurt, Germany |
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since 2015 |
Senior Lecturer in Haematology, Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, UK |
Honours and awards
Fellowships and Awards
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1990 |
Student Fellowship "Erasmus"by the EU – Strasbourg, France |
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1994 - 1996 |
Dr. Mildred Scheel International Fellowship (German Cancer Aid) |
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2005 |
Alfred und Angelika Gutermuth-Award for Leukaemia Research |
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2010 |
Heinrich und Erna Schauffler Award for Translational Tumor Research |
Academic positions
Degrees/Qualifications
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February 1993 |
Graduation in Medicine (grade 108/110), Università Perugia, Italy |
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February 1993 |
Doctoral degree (M.D.), Università Perugia, Italy |
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April 1993 |
Approbation as Physician by the Italian Ministry of Public Health, Rome, Italy, and the Landesprüfungsamt Baden Württemberg, Germany |
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May 2003 |
Habilitation for Experimental Medicine at Goethe University, Frankfurt, Germany |
Committees and reviewing
I led an International DFG funded Collaboration Research Group (German Israel Palestine) and was involved in setting up both National (German) Collaborative Research Groups (funding bodies: DFG; German Cancer Aid, Federal German and Regional Hesse Governments) as well International Collaboration (EU funded European Leukemia Network).
Journal Editing: Member of the Editorial Board of BMC Cancer (2010-2015).
Routinely Reviewing Manuscripts: Blood, Leukemia, Cancer Research, Clinical Cancer Research, Oncogene and several others.
Routinely Reviewing Grants: National (CR-UK, KKLF, Bloodwise) and International funding bodies (Deutsche Forschungsgemeinschaft – DFG, German Cancer Aid, José Carreras Leukemia Foundation, Wilhelm-Sander Foundation (all German), Associazione Ricerca e Lotta contro il Cancro (AIRC, Italy); INSERM (France), Austrian Academy of Science (Austria).
Contact Details
RuthardtM@cardiff.ac.uk
Main Hospital Building, Room Room 183, 7th floor B-C link, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Main Hospital Building, Room Room 183, 7th floor B-C link, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN