Professional background

Dr Marc Mansour is an honorary consultant haematologist at University College London Hospital and associate professor/research group leader at the UCL Cancer Institute.

He undertook his medical degree at the University of Edinburgh, medical training at King's College London and UCLH, followed by an MRC clinical research training PhDship in the laboratory of Professors David Linch and Rosemary Gale at UCL, where he studied notch signalling in acute leukaemia.

He was funded by the Kay Kendell Leukemia Research Fund to undertake a travelling fellowship at Harvard Medical School and Dana-Farber Cancer Institute in Boston, USA. He was awarded the HMS Claudia Adams Barr Innovative Research award, and was a Harvard Medical School faculty member from 2012-2014. He was funded through a Bennett senior fellowship (Blood Cancer UK) to establish his own research lab at the UCL Cancer Institute in 2014.

His research has focused on two aggressive haematological malignancies - T-cell acute lymphoblastic leukaemia (T-ALL) and acute myeloid leukaemia (AML). He has published extensively on the biology of acute leukaemia, authoring papers in Science, Nature, Nature Cell Biology, JCI, ELife, JCO and J Ex Med. His clinical interest is in ALL, AML and myelodysplasia (MDS).

Research interests

Dr Mansour has a long-standing interest in the biology and genetics of ALL and AML, particularly on the role of non-coding DNA in oncogene dysregulation. His translational research is aimed at developing novel therapies for patients with relapsed and refractory leukaemias.

https://www.ucl.ac.uk/cancer/research/department-haematology/leukaemia-biology/leukaemia-biology-research-group

Publications

1. Leon, T. E., Rapoz-D'Silva, T., Bertoli, C., Rahman, S., Magnussen, M., Philip, B., Farah, N., Richardson, S. E., Ahrabi, S., Guerra-Assuncao, J. A., Gupta, R., Nacheva, E. P., Henderson, S., Herrero, J., Linch, D. C., de Bruin, R. A. M. & Mansour, M. R. EZH2-Deficient T-cell Acute Lymphoblastic Leukemia Is Sensitized to CHK1 Inhibition through Enhanced Replication Stress. Cancer Discov 10, 998-1017, doi:10.1158/2159-8290.CD-19-0789 (2020).

2 Wilson, A. J., Troy-Barnes, E., Subhan, M., Clark, F., Gupta, R., Fielding, A. K., Kottaridis, P., Mansour, M. R., O'Nions, J., Payne, E., Chavda, N., Baker, R., Thomson, K. & Khwaja, A. Successful remission induction therapy with gilteritinib in a patient with de novo FLT3-mutated acute myeloid leukaemia and severe COVID-19. British journal of haematology, doi:10.1111/bjh.16962 (2020).

3 Hockings, C., Gohil, S., Dowse, R., Hoade, Y., Mansour, M. R., Gale, R. E., Linch, D. C., Rao, A. & Payne, E. M. In trans early mosaic mutational escape and novel phenotypic features of germline SAMD9 mutation. British journal of haematology, doi:10.1111/bjh.16322 (2020).

4 Rahman, S. & Mansour, M. R. The role of noncoding mutations in blood cancers. Dis Model Mech 12, doi:10.1242/dmm.041988 (2019).

5 Burt, R., Dey, A., Aref, S., Aguiar, M., Akarca, A., Bailey, K., Day, W., Hooper, S., Kirkwood, A., Kirschner, K., Lee, S. W., Lo Celso, C., Manji, J., Mansour, M. R., Marafioti, T., Mitchell, R. J., Muirhead, R. C., Cheuk Yan Ng, K., Pospori, C., Puccio, I., Zuborne-Alapi, K., Sahai, E. & Fielding, A. K. Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress. Blood 134, 1415-1429, doi:10.1182/blood.2019001398 (2019).

6 Armenteros-Monterroso, E., Zhao, L., Gasparoli, L., Brooks, T., Pearce, K., Mansour, M. R., Martens, J. H. A., de Boer, J. & Williams, O. The AAA+ATPase RUVBL2 is essential for the oncogenic function of c-MYB in acute myeloid leukemia. Leukemia, doi:10.1038/s41375-019-0495-8 (2019).

7 Gjini, E., Jing, C. B., Nguyen, A. T., Reyon, D., Gans, E., Kesarsing, M., Peterson, J., Pozdnyakova, O., Rodig, S. J., Mansour, M. R., Joung, K. & Look, A. T. Disruption of asxl1 results in myeloproliferative neoplasms in zebrafish. Dis Model Mech 12, doi:10.1242/dmm.035790 (2019).

8 Mansour, M. R., He, S., Li, Z., Lobbardi, R., Abraham, B. J., Hug, C., Rahman, S., Leon, T. E., Kuang, Y. Y., Zimmerman, M. W., Blonquist, T., Gjini, E., Gutierrez, A., Tang, Q., Garcia-Perez, L., Pike-Overzet, K., Anders, L., Berezovskaya, A., Zhou, Y., Zon, L. I., Neuberg, D., Fielding, A. K., Staal, F. J. T., Langenau, D. M., Sanda, T., Young, R. A. & Look, A. T. JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. The Journal of experimental medicine 215, 1929-1945, doi:10.1084/jem.20170484 (2018).

9 Farah, N., Kirkwood, A. A., Rahman, S., Leon, T., Jenkinson, S., Gale, R. E., Patrick, K., Hancock, J., Samarasinghe, S., Linch, D. C., Moorman, A. V., Goulden, N., Vora, A. & Mansour, M. R. Prognostic impact of the absence of biallelic deletion at the TRG locus for pediatric patients with T-cell acute lymphoblastic leukemia treated on the MRC UKALL2003 trial. Haematologica, doi:10.3324/haematol.2017.185801 (2018).

10 Lobbardi, R., Pinder, J., Martinez-Pastor, B., Theodorou, M., Blackburn, J. S., Abraham, B. J., Namiki, Y., Mansour, M., Abdelfattah, N. S., Molodtsov, A., Alexe, G., Toiber, D., de Waard, M., Jain, E., Boukhali, M., Lion, M., Bhere, D., Shah, K., Gutierrez, A., Stegmaier, K., Silverman, L. B., Sadreyev, R. I., Asara, J. M., Oettinger, M. A., Haas, W., Look, A. T., Young, R. A., Mostoslavsky, R., Dellaire, G. & Langenau, D. M. TOX regulates growth, DNA repair, and genomic instability in T-cell Acute Lymphoblastic Leukemia. Cancer Discov, doi:10.1158/2159-8290.CD-17-0267 (2017).

11 Rahman, S., Magnussen, M., Leon, T. E., Farah, N., Li, Z., Abraham, B. J., Alapi, K. Z., Mitchell, R. J., Naughton, T., Fielding, A. K., Pizzey, A., Bustraan, S., Allen, C., Popa, T., Pike-Overzet, K., Garcia-Perez, L., Gale, R. E., Linch, D. C., Staal, F. J., Young, R. A., Look, A. T. & Mansour, M. R. Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood, doi:10.1182/blood-2016-09-742148 (2017).

12 Li, Z., Abraham, B. J., Berezovskaya, A., Farah, N., Liu, Y., Leon, T., Fielding, A., Tan, S. H., Sanda, T., Weintraub, A. S., Li, B., Shen, S., Zhang, J., Mansour, M. R., Young, R. A. & Look, A. T. APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL. Leukemia, doi:10.1038/leu.2017.75 (2017).

13 Abraham, B. J., Hnisz, D., Weintraub, A. S., Kwiatkowski, N., Li, C. H., Li, Z., Weichert-Leahey, N., Rahman, S., Liu, Y., Etchin, J., Li, B., Shen, S., Lee, T. I., Zhang, J., Look, A. T., Mansour, M. R. & Young, R. A. Small genomic insertions form enhancers that misregulate oncogenes. Nature communications 8, 14385, doi:10.1038/ncomms14385 (2017).

14 He, S., Mansour, M. R., Zimmerman, M. W., Ki, D. H., Layden, H. M., Akahane, K., Gjini, E., de Groh, E. D., Perez-Atayde, A. R., Zhu, S., Epstein, J. A. & Look, A. T. Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain. eLife 5, doi:10.7554/eLife.14713 (2016).

15 Anderson, N. M., Li, D., Peng, H. L., Laroche, F. J., Mansour, M. R., Gjini, E., Aioub, M., Helman, D. J., Roderick, J. E., Cheng, T., Harrold, I., Samaha, Y., Meng, L., Amsterdam, A., Neuberg, D. S., Denton, T. T., Sanda, T., Kelliher, M. A., Singh, A., Look, A. T. & Feng, H. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia 30, 1365-1374, doi:10.1038/leu.2016.26 (2016).

16 Mansour, M. R., Abraham, B. J., Anders, L., Berezovskaya, A., Gutierrez, A., Durbin, A. D., Etchin, J., Lawton, L., Sallan, S. E., Silverman, L. B., Loh, M. L., Hunger, S. P., Sanda, T., Young, R. A. & Look, A. T. Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science 346, 1373-1377, doi:10.1126/science.1259037 (2014).

17 Etchin, J., Montero, J., Berezovskaya, A., Le, B. T., Kentsis, A., Christie, A. L., Conway, A. S., Chen, W. C., Reed, C., Mansour, M. R., Ng, C. E., Adamia, S., Rodig, S. J., Galinsky, I. A., Stone, R. M., Klebanov, B., Landesman, Y., Kauffman, M., Shacham, S., Kung, A. L., Wang, J. C., Letai, A. & Look, A. T. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia, doi:10.1038/leu.2015.194 (2015).

18 Akahane, K., Sanda, T., Mansour, M. R., Radimerski, T., DeAngelo, D. J., Weinstock, D. M. & Look, A. T. HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia. Leukemia, doi:10.1038/leu.2015.222 (2015).

19 Lobry, C., Oh, P., Mansour, M. R., Look, A. T. & Aifantis, I. Notch signaling: switching an oncogene to a tumor suppressor. Blood 123, 2451-2459, doi:10.1182/blood-2013-08-355818 (2014).

20 Barcelo, C., Etchin, J., Mansour, M. R., Sanda, T., Ginesta, M. M., Sanchez-Arevalo Lobo, V. J., Real, F. X., Capella, G., Estanyol, J. M., Jaumot, M., Look, A. T. & Agell, N. Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells. Gastroenterology 147, 882-892 e888, doi:10.1053/j.gastro.2014.06.041 (2014).

21 Li, N., Fassl, A., Chick, J., Inuzuka, H., Li, X., Mansour, M. R., Liu, L., Wang, H., King, B., Shaik, S., Gutierrez, A., Ordureau, A., Otto, T., Kreslavsky, T., Baitsch, L., Bury, L., Meyer, C. A., Ke, N., Mulry, K. A., Kluk, M. J., Roy, M., Kim, S., Zhang, X., Geng, Y., Zagozdzon, A., Jenkinson, S., Gale, R. E., Linch, D. C., Zhao, J. J., Mullighan, C. G., Harper, J. W., Aster, J. C., Aifantis, I., von Boehmer, H., Gygi, S. P., Wei, W., Look, A. T. & Sicinski, P. Cyclin C is a haploinsufficient tumour suppressor. Nature cell biology 16, 1080-1091, doi:10.1038/ncb3046 (2014).

22 Gjini, E., Mansour, M. R., Sander, J. D., Moritz, N., Nguyen, A. T., Kesarsing, M., Gans, E., He, S., Chen, S., Ko, M., Kuang, Y. Y., Yang, S., Zhou, Y., Rodig, S., Zon, L. I., Joung, J. K., Rao, A. & Look, A. T. A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing. Molecular and cellular biology 35, 789-804, doi:10.1128/MCB.00971-14 (2015).

23 Anderson, N. M., Harrold, I., Mansour, M. R., Sanda, T., McKeown, M., Nagykary, N., Bradner, J. E., Lan Zhang, G., Look, A. T. & Feng, H. BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T-ALL cell lines. Leukemia 28, 1145-1148, doi:10.1038/leu.2013.377 (2014).

24 Mansour, M. R., Reed, C., Eisenberg, A. R., Tseng, J. C., Twizere, J. C., Daakour, S., Yoda, A., Rodig, S. J., Tal, N., Shochat, C., Berezovskaya, A., DeAngelo, D. J., Sallan, S. E., Weinstock, D. M., Izraeli, S., Kung, A. L., Kentsis, A. & Look, A. T. Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia. British journal of haematology 168, 230-238, doi:10.1111/bjh.13115 (2015).

25 Shochat, C., Tal, N., Gryshkova, V., Birger, Y., Bandapalli, O. R., Cazzaniga, G., Gershman, N., Kulozik, A. E., Biondi, A., Mansour, M. R., Twizere, J. C., Muckenthaler, M. U., Ben-Tal, N., Constantinescu, S. N., Bercovich, D. & Izraeli, S. Novel activating mutations lacking cysteine in type I cytokine receptors in acute lymphoblastic leukemia. Blood 124, 106-110, doi:10.1182/blood-2013-10-529685 (2014).

26 Mansour, M. R., Sanda, T., Lawton, L. N., Li, X., Kreslavsky, T., Novina, C. D., Brand, M., Gutierrez, A., Kelliher, M. A., Jamieson, C. H., von Boehmer, H., Young, R. A. & Look, A. T. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. The Journal of experimental medicine 210, 1545-1557, doi:10.1084/jem.20122516 (2013).

27 Etchin, J., Sanda, T., Mansour, M. R., Kentsis, A., Montero, J., Le, B. T., Christie, A. L., McCauley, D., Rodig, S. J., Kauffman, M., Shacham, S., Stone, R., Letai, A., Kung, A. L. & Thomas Look, A. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. British journal of haematology 161, 117-127, doi:10.1111/bjh.12231 (2013).

28 Shepherd, C., Banerjee, L., Cheung, C. W., Mansour, M. R., Jenkinson, S., Gale, R. E. & Khwaja, A. PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response. Leukemia 27, 650-660, doi:10.1038/leu.2012.285 (2013).

29 Etchin, J., Sun, Q., Kentsis, A., Farmer, A., Zhang, Z. C., Sanda, T., Mansour, M. R., Barcelo, C., McCauley, D., Kauffman, M., Shacham, S., Christie, A. L., Kung, A. L., Rodig, S. J., Chook, Y. M. & Look, A. T. Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, doi:10.1038/leu.2012.219 (2012).

30 Jenkinson, S., Koo, K., Mansour, M. R., Goulden, N., Vora, A., Mitchell, C., Wade, R., Richards, S., Hancock, J., Moorman, A. V., Linch, D. C. & Gale, R. E. Impact of NOTCH1/FBXW7 mutations on outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on the MRC UKALL 2003 trial. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, doi:10.1038/leu.2012.176 (2012).

31 Mansour, M. R. & Look, A. T. Discovery of a secreted tumor suppressor provides a promising therapeutic strategy for follicular lymphoma. Cancer cell 20, 559-561, doi:10.1016/j.ccr.2011.10.027 (2011).

32 Gutierrez, A., Grebliunaite, R., Feng, H., Kozakewich, E., Zhu, S., Guo, F., Payne, E., Mansour, M., Dahlberg, S. E., Neuberg, D. S., den Hertog, J., Prochownik, E. V., Testa, J. R., Harris, M., Kanki, J. P. & Look, A. T. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. The Journal of experimental medicine 208, 1595-1603, doi:10.1084/jem.20101691 (2011).

33 Mansour, M. R., Sulis, M. L., Duke, V., Foroni, L., Jenkinson, S., Koo, K., Allen, C. G., Gale, R. E., Buck, G., Richards, S., Paietta, E., Rowe, J. M., Tallman, M. S., Goldstone, A. H., Ferrando, A. A. & Linch, D. C. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol 27, 4352-4356, doi:10.1200/JCO.2009.22.0996 (2009).

34 Tosello, V., Mansour, M. R., Barnes, K., Paganin, M., Sulis, M. L., Jenkinson, S., Allen, C. G., Gale, R. E., Linch, D. C., Palomero, T., Real, P., Murty, V., Yao, X., Richards, S. M., Goldstone, A., Rowe, J., Basso, G., Wiernik, P. H., Paietta, E., Pieters, R., Horstmann, M., Meijerink, J. P. & Ferrando, A. A. WT1 mutations in T-ALL. Blood 114, 1038-1045 (2009).

35 Marks, D. I., Paietta, E. M., Moorman, A. V., Richards, S. M., Buck, G., DeWald, G., Ferrando, A., Fielding, A. K., Goldstone, A. H., Ketterling, R. P., Litzow, M. R., Luger, S. M., McMillan, A. K., Mansour, M. R., Rowe, J. M., Tallman, M. S. & Lazarus, H. M. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood 114, 5136-5145, doi:10.1182/blood-2009-08-231217 (2009).

36 Howe, S. J., Mansour, M. R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., Brugman, M. H., Pike-Overzet, K., Chatters, S. J., de, R. D., Gilmour, K. C., Adams, S., Thornhill, S. I., Parsley, K. L., Staal, F. J., Gale, R. E., Linch, D. C., Bayford, J., Brown, L., Quaye, M., Kinnon, C., Ancliff, P., Webb, D. K., Schmidt, M., von, K. C., Gaspar, H. B. & Thrasher, A. J. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J.Clin.Invest 118, 3143-3150 (2008).

37 Gordon, W. R., Roy, M., Vardar-Ulu, D., Garfinkel, M., Mansour, M. R., Aster, J. C. & Blacklow, S. C. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood 113, 4381-4390 (2009).

38 Mansour, M. R. Oncogenic Kras and Notch-1 cooperate in T-cell acute lymphoblastic leukemia/lymphoma. Expert Rev Hematol 2, 133-136, doi:10.1586/ehm.09.3 (2009).

39 Mansour, M. R., Duke, V., Foroni, L., Patel, B., Allen, C. G., Ancliff, P. J., Gale, R. E. & Linch, D. C. Notch-1 mutations are secondary events in some patients with T-cell acute lymphoblastic leukemia. Clin.Cancer Res. 13, 6964-6969 (2007).

40 Maser, R. S., Choudhury, B., Campbell, P. J., Feng, B., Wong, K. K., Protopopov, A., O'Neil, J., Gutierrez, A., Ivanova, E., Perna, I., Lin, E., Mani, V., Jiang, S., McNamara, K., Zaghlul, S., Edkins, S., Stevens, C., Brennan, C., Martin, E. S., Wiedemeyer, R., Kabbarah, O., Nogueira, C., Histen, G., Aster, J., Mansour, M., Duke, V., Foroni, L., Fielding, A. K., Goldstone, A. H., Rowe, J. M., Wang, Y. A., Look, A. T., Stratton, M. R., Chin, L., Futreal, P. A. & DePinho, R. A. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447, 966-971, doi:10.1038/nature05886 (2007).

41 Mansour, M. R., Linch, D. C., Foroni, L., Goldstone, A. H. & Gale, R. E. High incidence of Notch-1 mutations in adult patients with T-cell acute lymphoblastic leukemia. Leukemia 20, 537-539 (2006).

42 Direkze, S., Mansour, M., Rodriguez-Justo, M., Kibbler, C., Gant, V. & Peggs, K. S. Candida kefyr fungal enteritis following autologous BMT. Bone Marrow Transplant 47, 465-466, doi:10.1038/bmt.2011.112 (2012).

43 Mansour, M. R., Dogan, A., Morris, E. C., Khwaja, A., Linch, D. C., Mackinnon, S. & Peggs, K. S. Allogeneic transplantation for hepatosplenic alphabeta T-cell lymphoma. Bone Marrow Transplant. 35, 931-934 (2005).