Contact

  • Kay Kendall Intermediate Fellow

n.crump@imperial.ac.uk

Areas of Research

Epigenetic regulation of myeloma

Multiple myeloma is in many ways a disease driven by inappropriate gene expression. It is characterised by the aberrant activation of gene regulatory elements known as enhancers, stimulating the upregulation of key oncogenes. Blocking this behaviour is therefore a promising strategy for myeloma treatment, and many therapeutic strategies directly or indirectly target gene regulatory pathways.

The lab studies the epigenetic regulation of gene expression, focused on the way these processes are dysregulated in multiple myeloma. We have a particular interest in understanding the role of oncogenic enhancer activity in driving myeloma-specific transcriptional profiles, and identifying the factors responsible for this behaviour. A major goal of the lab is to identify potential therapeutic targets that could be developed as novel therapies for multiple myeloma.

We use a variety of high-throughput genomics techniques to study the chromatin landscape, including ChIP-seq, ATAC-seq and RNA-seq. We have optimised TOPmentation, a small cell-number technique that allows us to characterise the chromatin profile of myeloma patient samples. In addition, we use the 3C technology Micro-Capture-C to map the physical association of enhancers and promoters. By combining these techniques with genetic and pharmacological manipulation of myeloma cell lines, we are able to explore mechanistically enhancer function and regulation.

Mechanisms of myeloma drug resistance

Relapse is very common in myeloma after initial treatment. Patients typically enter remission following treatment, but invariably relapse, often with resistance to one or more of these drugs. There is therefore a pressing need to understand the mechanisms that drive this resistance to find ways to counteract it. We are working to identify and understand epigenetic mechanisms that drive drug resistance via changes in gene expression, which therefore may be reversed to resensitise cells to therapy.

Our team

Nick Crump (he/him)

Jinglin Zhou (he/him)

Jinglin Zhou (he/him)
PhD student

Jason Taslim (he/him)

Jason Taslim (he/him)
Research assistant

Sophie Ball (she/her)

Sophie Ball (she/her)
PhD student

Funders

Research Publications

Citation

BibTex format

@article{Rajhansa:2026:10.1016/j.exphem.2026.105458,
author = {Rajhansa, S and Crump, NT and Khoo, HM and Dopico-Fernandez, A and Bozhilov, Y and Brennan, PE and Fedorov, O and Adams, C and Farnie, G and Milne, TA and Wilkinson, AC},
doi = {10.1016/j.exphem.2026.105458},
journal = {Exp Hematol},
title = {Inhibition of MLLT1 Limits Growth of KMT2A::AFF1 Leukemias Without Killing Healthy Hematopoietic Stem Cells.},
url = {http://dx.doi.org/10.1016/j.exphem.2026.105458},
volume = {160},
year = {2026}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A major challenge in cancer therapeutics has been the identification of targets that are selectively toxic to cancer cells while displaying limited effects on healthy counterparts. Toxicities related to blood production from hematopoietic stem and progenitor cells (HSPCs) can be particularly problematic and can result in patient morbidity and mortality. MLLT1 has been identified as a key potential target in acute myeloid leukemia. Here, we evaluated the sensitivity of the MLLT1 inhibitor SGC-iMLLT using a panel of leukemia cell lines and healthy HSPCs. We found that SGC-iMLLT downregulated MLLT1 target genes and strongly inhibited KMT2A::AFF1-driven leukemia growth in vitro and in vivo. By contrast, SGC-iMLLT did not alter in vitro colony forming potential of human HSPCs or affect long-term in vivo function of mouse HSPCs. These results suggest that SGC-iMLLT may have a promising therapeutic window in the treatment of KMT2A::AFF1-driven leukemias and that further clinical development is warranted.
AU  - Rajhansa,S
AU  - Crump,NT
AU  - Khoo,HM
AU  - Dopico-Fernandez,A
AU  - Bozhilov,Y
AU  - Brennan,PE
AU  - Fedorov,O
AU  - Adams,C
AU  - Farnie,G
AU  - Milne,TA
AU  - Wilkinson,AC
DO  - 10.1016/j.exphem.2026.105458
PY  - 2026///
TI  - Inhibition of MLLT1 Limits Growth of KMT2A::AFF1 Leukemias Without Killing Healthy Hematopoietic Stem Cells.
T2  - Exp Hematol
UR  - http://dx.doi.org/10.1016/j.exphem.2026.105458
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42242459
VL  - 160
ER  -
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