Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories

Kellaway, Sophie G; Keane, Peter; Edginton-White, Benjamin; Regha, Kakkad; Kennett, Ella; Bonifer, Constanze

doi:10.26508/lsa.202000864

All Outputs (9)

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1 (2024)
Journal Article
Coleman, D. J., Keane, P., Chin, P. S., Ames, L., Kellaway, S., Blair, H., Khan, N., Griffin, J., Holmes, E., Maytum, A., Potluri, S., Strate, L., Koscielniak, K., Raghavan, M., Bushweller, J., Heidenreich, O., Rabbitts, T., Cockerill, P. N., & Bonifer, C. (2024). Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1. iScience, 27(4), Article 109576. https://doi.org/10.1016/j.isci.2024.109576

AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse an... Read More about Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1.

Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth (2024)
Journal Article
Kellaway, S. G., Potluri, S., Keane, P., Blair, H. J., Ames, L., Worker, A., Chin, P. S., Ptasinska, A., Derevyanko, P. K., Adamo, A., Coleman, D. J. L., Khan, N., Assi, S. A., Krippner-Heidenreich, A., Raghavan, M., Cockerill, P. N., Heidenreich, O., & Bonifer, C. (2024). Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth. Nature Communications, 15(1), Article 1359. https://doi.org/10.1038/s41467-024-45691-4

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cel... Read More about Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth.

Gene regulation in t(6;9) DEK::NUP214 Acute Myeloid Leukemia resembles that of FLT3-ITD/NPM1 Acute Myeloid Leukemia but with an altered HOX/MEIS axis (2024)
Journal Article
Potluri, S., Kellaway, S. G., Coleman, D. J. L., Keane, P., Imperato, M. R., Assi, S. A., Cockerill, P. N., & Bonifer, C. (2024). Gene regulation in t(6;9) DEK::NUP214 Acute Myeloid Leukemia resembles that of FLT3-ITD/NPM1 Acute Myeloid Leukemia but with an altered HOX/MEIS axis. Leukemia, 38(2), 403–407. https://doi.org/10.1038/s41375-023-02118-1

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth (2023)
Journal Article
Coleman, D. J., Keane, P., Luque-Martin, R., Chin, P. S., Blair, H., Ames, L., Kellaway, S. G., Griffin, J., Holmes, E., Potluri, S., Assi, S. A., Bushweller, J., Heidenreich, O., Cockerill, P. N., & Bonifer, C. (2023). Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth. Cell Reports, 42(12), Article 113568. https://doi.org/10.1016/j.celrep.2023.113568

Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene... Read More about Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.

A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification (2023)
Journal Article
Edginton-White, B., Maytum, A., Kellaway, S. G., Goode, D. K., Keane, P., Pagnuco, I., Assi, S. A., Ames, L., Clarke, M., Cockerill, P. N., Göttgens, B., Cazier, J. B., & Bonifer, C. (2023). A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification. Nature Communications, 14(1), Article 267. https://doi.org/10.1038/s41467-023-35910-9

Developmental control of gene expression critically depends on distal cis-regulatory elements including enhancers which interact with promoters to activate gene expression. To date no global experiments have been conducted that identify their cell ty... Read More about A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification.

Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia (2022)
Journal Article
Adamo, A., Chin, P., Keane, P., Assi, S. A., Potluri, S., Kellaway, S. G., Coleman, D., Ames, L., Ptasinska, A., Delwel, H. R., Cockerill, P. N., & Bonifer, C. (2023). Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia. Leukemia, 37(1), 102-112. https://doi.org/10.1038/s41375-022-01744-5

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by mutations in genes encoding transcriptional and epigenetic regulators together with signaling genes. It is characterized by a disturbance of differentiation and abnorm... Read More about Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia.

Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia (2022)
Journal Article
Tirtakusuma, R., Szoltysek, K., Milne, P., Grinev, V. V., Ptasinska, A., Chin, P. S., Meyer, C., Nakjang, S., Hehir-Kwa, J. Y., Williamson, D., Cauchy, P., Keane, P., Assi, S. A., Ashtiani, M., Kellaway, S. G., Imperato, M. R., Vogiatzi, F., Schweighart, E. K., Lin, S., Wunderlich, M., …Bomken, S. (2022). Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia. Blood, 140(17), 1875-1890. https://doi.org/10.1182/blood.2021015036

The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukemia, resulting in poor clinical outcomes caused by resistance to... Read More about Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia.

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal (2022)
Journal Article
Schnoeder, T. M., Schwarzer, A., Jayavelu, A. K., Hsu, C.-J., Kirkpatrick, J., Döhner, K., Perner, F., Eifert, T., Huber, N., Arreba-Tutusaus, P., Dolnik, A., Assi, S. A., Nafria, M., Jiang, L., Dai, Y.-T., Chen, Z., Chen, S.-J., Kellaway, S. G., Ptasinska, A., Ng, E. S., …Heidel, F. H. (2022). PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. Blood, 139(7), 1080-1097. https://doi.org/10.1182/blood.2021012778

In an effort to identify novel drugs targeting fusion-oncogene–induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C (PLC) signaling. We iden... Read More about PLCG1 is required for AML1-ETO leukemia stem cell self-renewal.

Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories (2021)
Journal Article
Kellaway, S. G., Keane, P., Edginton-White, B., Regha, K., Kennett, E., & Bonifer, C. (2021). Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories. Life Science Alliance, 4(2), Article e202000864. https://doi.org/10.26508/lsa.202000864

Mutations of the haematopoietic master regulator RUNX1 are associated with acute myeloid leukaemia, familial platelet disorder and other haematological malignancies whose phenotypes and prognoses depend upon the class of the RUNX1 mutation. The bioch... Read More about Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories.