Sud, A., Morilla, R., Ethell, M., Taussig, D. & Liapis, K.
(2015). Green-grey crystals in acute myeloid leukaemia. British journal of haematology,
Miraki-Moud, F., Ghazaly, E., Ariza-McNaughton, L., Hodby, K.A., Clear, A., Anjos-Afonso, F., Liapis, K., Grantham, M., Sohrabi, F., Cavenagh, J., et al.
(2015). Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo. Blood,
Most AMLs lack ASS1, which allows synthesis of arginine, and so depend on exogenous sources. Depletion of arginine via ADI-PEG 20 reduces the burden of primary AML in vivo and in vitro..
Liapis, K., Taussig, D., Cotter, F.E. & Gribben, J.G.
(2014). Cutaneous cryptococcosis in Hodgkin lymphoma. British journal of haematology,
Griessinger, E., Anjos-Afonso, F., Pizzitola, I., Rouault-Pierre, K., Vargaftig, J., Taussig, D., Gribben, J., Lassailly, F. & Bonnet, D.
(2014). A Niche-Like Culture System Allowing the Maintenance of Primary Human Acute Myeloid Leukemia-Initiating Cells: A New Tool to Decipher Their Chemoresistance and Self-Renewal Mechanisms. Stem cells translational medicine,
Liapis, K., Chung, Y., Akhtar, W. & Taussig, D.
(2014). A patient with rheumatoid arthritis, cryoglobulinaemia, and an "accidental" finding. Bmj,
Manodoro, F., Marzec, J., Chaplin, T., Miraki-Moud, F., Moravcsik, E., Jovanovic, J.V., Wang, J., Iqbal, S., Taussig, D., Grimwade, D., et al.
(2014). Loss of imprinting at the 14q32 domain is associated with microRNA overexpression in acute promyelocytic leukemia. Blood,
Loss of imprinting occurs at the 14q32 domain in APL. DNA methylation at the CTCF binding sites correlates with the overexpression of 14q32 miRNAs..
Davies, J.K., Taussig, D., Oakervee, H., Smith, M., Agrawal, S., Cavenagh, J.D. & Gribben, J.G.
(2013). Long-term survival with low toxicity after allogeneic transplantation for acute myeloid leukaemia and myelodysplasia using non-myeloablative conditioning without T cell depletion. British journal of haematology,
Anjos-Afonso, F., Currie, E., Palmer, H.G., Foster, K.E., Taussig, D.C. & Bonnet, D.
(2013). CD34− Cells at the Apex of the Human Hematopoietic Stem Cell Hierarchy Have Distinctive Cellular and Molecular Signatures. Cell stem cell,
Rouault-Pierre, K., Lopez-Onieva, L., Foster, K., Anjos-Afonso, F., Lamrissi-Garcia, I., Serrano-Sanchez, M., Mitter, R., Ivanovic, Z., de Verneuil, H., Gribben, J., et al.
(2013). HIF-2α Protects Human Hematopoietic Stem/Progenitors and Acute Myeloid Leukemic Cells from Apoptosis Induced by Endoplasmic Reticulum Stress. Cell stem cell,
Miraki-Moud, F., Anjos-Afonso, F., Hodby, K.A., Griessinger, E., Rosignoli, G., Lillington, D., Jia, L., Davies, J.K., Cavenagh, J., Smith, M., et al.
(2013). Acute myeloid leukemia does not deplete normal hematopoietic stem cells but induces cytopenias by impeding their differentiation. Proceedings of the national academy of sciences,
Vargaftig, J., Taussig, D.C., Griessinger, E., Anjos-Afonso, F., Lister, T.A., Cavenagh, J., Oakervee, H., Gribben, J. & Bonnet, D.
(2012). Frequency of leukemic initiating cells does not depend on the xenotransplantation model used. Leukemia,
Joshi, N.M., Hassan, S., Jasani, P., Dixon, S., Cavenagh, J.D., Oakervee, H.E., Smith, M., Agrawal, S.A., Auer, R., de Vos, J., et al.
(2012). Bile acid malabsorption in patients with graft-versus-host disease of the gastrointestinal tract. British journal of haematology,
Auer, R.L., MacDougall, F., Oakervee, H.E., Taussig, D., Davies, J.K., Syndercombe-Court, D., Agrawal, S., Cavenagh, J.D., Lister, T.A. & Gribben, J.G., et al.
(2012). T-cell replete fludarabine/cyclophosphamide reduced intensity allogeneic stem cell transplantation for lymphoid malignancies. British journal of haematology,
Farren, T.W., Giustiniani, J., Liu, F.-., Tsitsikas, D.A., Macey, M.G., Cavenagh, J.D., Oakervee, H.E., Taussig, D., Newland, A.C., Calaminici, M., et al.
(2011). Differential and tumor-specific expression of CD160 in B-cell malignancies. Blood,
CD160 is a human natural killer (NK)-cell–activating receptor that is also expressed on T-cell subsets. In the present study, we examined 811 consecutive cases of B-cell lymphoproliferative disorders (B-LPDs), and demonstrated CD160 expression in 98% (590 of 600) of chronic lymphocytic leukemia (CLL) cases, 100% (32 of 32) of hairy cell leukemia (HCL) cases, 15% (5 of 34) of mantle cell lymphoma (MCL) in the leukemic phase, and 16% (23 of 145) of other B-LPD cases. CD160 transcript and protein were absent in the normal B-cell hierarchy, from stem cells, B-cell precursors, maturing B cells in the germinal center, and circulating B cells, including CD5+CD19+ B1 cells in umbilical cord. CD160 positivity was significantly higher in CLL and HCL in terms of percentage (65.9% and 67.8%, respectively, P < .0001) and median fluorescence intensity (552 and 857, respectively, P < .0001) compared with all other B-LPD cases. Lymph node CLL samples were also CD160+. Using the disease-specific expression of CD5, CD23, and CD160, a score of 3 characterized CLL (diagnostic odds ratio, 1430); a score of 0 excluded CLL, MCL, and HCL; and the CD23/CD5 ratio differentiated CLL from leukemic CD23+ MCL. In the B-cell lineage, CD160 is a tumor-specific antigen known to mediate cellular activation signals in CLL, and is a novel target for therapeutic manipulation and monitoring of minimal residual disease..
Taussig, D.C., Vargaftig, J., Miraki-Moud, F., Griessinger, E., Sharrock, K., Luke, T., Lillington, D., Oakervee, H., Cavenagh, J., Agrawal, S.G., et al.
(2010). Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34− fraction. Blood,
Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34+ fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34+ fraction. We transplanted sorted fractions of primary NPM-mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately one-half of cases had LICs exclusively within the CD34− fraction, whereas the CD34+ fraction contained normal multilineage hematopoietic repopulating cells. Most of the remaining cases had LICs in both CD34+ and CD34− fractions. When samples were sorted based on CD34 and CD38 expression, multiple fractions initiated leukemia in primary and secondary recipients. The data indicate that the phenotype of LICs is more heterogeneous than previously realized and can vary even within a single sample. This feature of LICs may make them particularly difficult to eradicate using therapies targeted against surface antigens..
Le Dieu, R., Taussig, D., Lister, T.A. & Gribben, J.G.
(2009). Negative immunomagnetic selection of T cells from peripheral blood of presentation AML specimens. Journal of immunological methods,
Anjos-Afonso, F., Taussig, D. & Bonnet, D.
(2009). PERTURBED BONE MARROW MESENCHYMAL STROMAL (MSC) COMPARTMENT IN AML PATIENTS: IMPLICATION FOR UNDERSTANDING LEUKEMIC MICROENVIRONMENT. Experimental hematology,
Le Dieu, R., Taussig, D.C., Ramsay, A.G., Mitter, R., Miraki-Moud, F., Fatah, R., Lee, A.M., Lister, T.A. & Gribben, J.G.
(2009). Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood,
Understanding how the immune system in patients with cancer interacts with malignant cells is critical for the development of successful immunotherapeutic strategies. We studied peripheral blood from newly diagnosed patients with acute myeloid leukemia (AML) to assess the impact of this disease on the patients' T cells. The absolute number of peripheral blood T cells is increased in AML compared with healthy controls. An increase in the absolute number of CD3+56+ cells was also noted. Gene expression profiling on T cells from AML patients compared with healthy donors demonstrated global differences in transcription suggesting aberrant T-cell activation patterns. These gene expression changes differ from those observed in chronic lymphocytic leukemia (CLL), indicating the heterogeneous means by which different tumors evade the host immune response. However, in common with CLL, differentially regulated genes involved in actin cytoskeletal formation were identified, and therefore the ability of T cells from AML patients to form immunologic synapses was assessed. Although AML T cells could form conjugates with autologous blasts, their ability to form immune synapses and recruit phosphotyrosine signaling molecules to the synapse was significantly impaired. These findings identify T-cell dysfunction in AML that may contribute to the failure of a host immune response against leukemic blasts..
Taussig, D.C., Miraki-Moud, F., Anjos-Afonso, F., Pearce, D.J., Allen, K., Ridler, C., Lillington, D., Oakervee, H., Cavenagh, J., Agrawal, S.G., et al.
(2008). Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood,
Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemia-initiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome-conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34(+)CD38(+) fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemia-initiating cell capacity. This study highlights the potential pitfall of antibody-mediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested..
Le Dieu, R., Ramsay, A.G., Taussig, D., Mitter, R. & Gribben, J.G.
(2008). Differential Gene Expression Profile Identifies the Nature of T Cell Defects in AML Patients at Diagnosis. Blood,
Pearce, D.J., Taussig, D., Zibara, K., Smith, L.-., Ridler, C.M., Preudhomme, C., Young, B.D., Rohatiner, A.Z., Lister, T.A. & Bonnet, D., et al.
(2006). AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML. Blood,
The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and nonengrafters. FLT3 internal tandem duplication (ITD) and nucleophosmin mutations occurred at a similar frequency in engrafters and nonengrafters. The only variable that was related to engraftment ability was the karyotypically defined risk stratification of individual AML cases. Of interest, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID engrafting and nonengrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning, or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response..
Pearce, D., Taussig, D. & Bonnet, D.
(2006). Implications of the Expression of Myeloid Markers on Normal and Leukemic Stem Cells. Cell cycle,
Davies, J.K., Taussig, D.C., Oakervee, H., Davies, A.J., Agrawal, S.G., Gribben, J.G., Lister, T.A. & Cavenagh, J.D.
(2006). Long-Term Follow-Up After Reduced-Intensity Conditioning Allogeneic Transplantation for Acute Myeloid Leukemia/Myelodysplastic Syndrome: Late CNS Relapses Despite Graft-Versus-Host Disease. Journal of clinical oncology,
Pearce, D.J., Taussig, D., Simpson, C., Allen, K., Rohatiner, A.Z., Lister, T.A. & Bonnet, D.
(2005). Characterization of Cells with a High Aldehyde Dehydrogenase Activity from Cord Blood and Acute Myeloid Leukemia Samples. Stem cells,
Taussig, D.C., Pearce, D.J., Simpson, C., Rohatiner, A.Z., Lister, T.A., Kelly, G., Luongo, J.L., Danet-Desnoyers, G.A. & Bonnet, D.
(2005). Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood,
Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that nonobese diabetic/severe combined immunodeficiency (NOD/SCID) leukemia-initiating cells (SL-ICs) are restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from an HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing..
(2003). Durable remissions of myelodysplastic syndrome and acute myeloid leukemia after reduced-intensity allografting. J clin oncol,
(2002). Sternal osteomyelitis caused by Aspergillus fumigatus in a patient with previously treated Hodgkin's disease. Journal of clinical pathology,
Longhurst, H.J., Taussig, D., Haque, T., Court, D.S., Cavenagh, J., Edgar, J.D. & Helbert, M.R.
(2002). Non-myeloablative bone marrow transplantation in an adult with Wiskott-Aldrich syndrome. British journal of haematology,
(2002). Male Cells in Female Recipients of Hematopoietic-Cell Transplants. New england journal of medicine,
(1997). Effect of Atenolol on Mortality and Cardiovascular Morbidity after Noncardiac Surgery. New england journal of medicine,