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• Journal article
  Lau I-J, Bloye G, Smith AL, Harman J, Hamley JC, Sharlandjieva V, Denny NDR, Chahrour C, Li H, Jackson N, Vyas P, Davies J, Hughes JR, Crump N, Milne TAet al., 2026,

  MYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemia.

  , Blood

  Aberrant enhancer usage is a defining feature of oncogenic transcriptional reprogramming. Therapeutic strategies that disrupt enhancer-driven gene regulation may offer new treatment avenues. MYB is a key hematopoietic transcription factor that is frequently dysregulated in a broad range of cancers and plays a critical role in sustaining malignant cell states, including in aggressive leukemia subtypes such as KMT2A-rearranged (KMT2A-r) leukemias. The molecular mechanisms by which it maintains oncogenic transcription remain incompletely understood. Here, we investigate the role of MYB in directing pathological enhancer activity to drive oncogene expression in leukemia. Using high-resolution Micro-Capture-C, we show that upon MYB degradation, highly defined enhancer-promoter interactions at MYB binding sites are lost, correlating with significant downregulation of target gene expression. When anchored to a gene desert region, the Myb transactivation domain (MybTA) is sufficient and necessary for nucleation of an enhancer-like region. Critically, long-range chromatin interactions are established up to 400 kb away from where MybTA is anchored. This results in the activation of transcription from distal cryptic elements, which is reduced or abolished in the presence of point mutations that disrupt its interaction with the co-activators P300/CBP. Together, these results indicate that MYB activity alone is sufficient to generate an enhancer, inducing transcription through precise enhancer-promoter crosstalk, and identify the MYB-P300/CBP axis as a therapeutically actionable vulnerability in enhancer-driven malignancies.

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• Journal article
  Ng HL, Burt R, Feldhahn N, 2026,

  BCR::ABL1-induced enhancer reprogramming uncovers hypersensitivity of Ph+ B-ALL cells to enhancer-targeting drugs

  , Advanced Science, ISSN: 2198-3844
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• Journal article
  Zhou J, Crump NT, Román-Trufero M, Auner HWet al., 2026,

  TIME-RESOLVED MULTI-LAYERED PROFILING IDENTIFIES RESOLUTION OF RIBOSOME COLLISIONS AND TRANSLATIONAL RECOVERY AS MECHANISMS CONTRIBUTING TO PROTEASOME INHIBITOR RESISTANCE

  , Haematologica, Vol: 111, Pages: 1-1, ISSN: 0390-6078

  Background. Multiple myeloma (MM) is characterised by a high dependence on intracellular protein homeostasis (proteostasis), a vulnerability exploited therapeutically by proteasome inhibitors (PIs) that disrupt protein degradation and induce proteotoxic stress. PIs have significantly improved clinical outcomes, but molecular mechanisms underlying adaptive resistance of MM cells to PI-induced stress remain incompletely understood. Ribosome collisions (RCs) are events that occur during compromised mRNA translation when ribosomes slow or pause, causing trailing ribosomes to physically collide. This triggers translational stress signaling aimed at resolving RCs and restoring homeostatic protein synthesis. Whether proteasome inhibition induces RCs in MM cells and whether RC resolution mechanisms contribute to adaptive PI resistance remains unknown. Methods. MM cell lines were exposed to a short pulse of carfilzomib (Cfz) to mimic clinical pharmacokinetics and followed by multi-omic analyses. RNA-seq and ribosome profiling (ribo-seq) were performed at 4h (acute stress), 24-48h (early recovery) and 6 days (late recovery) post-treatment. Global protein synthesis was assessed by puromycin incorporation, intracellular amino acid levels were quantified by targeted metabolomics (LC-MS/MS), and changes in gene and protein expression and phosphorylation were analysed by qRT-PCR and immunoblotting. Results. Cfz rapidly induced RCs, activation of the ZAKalpha-P38 initiated ribotoxic stress response (RSR), reduction of amino acids, activation of the integrated stress response (ISR) and suppression of global protein synthesis. Despite this translational repression, ribo-seq revealed selective enhancement of translation of proteasome subunits and stress-response genes in line with a “proteasome bounce-back” mechanism. During the 24h-48h period, RCs were resolved and both RSR and ISR signalling progressively decreased. Simultaneously, global protein synthesis recovered and

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• Journal article
  Smith AL, Denny N, Chahrour C, Sharp K, Arachi M, Dopico-Fernandez AM, Elliott N, Harman JR, Jackson T, Geng H, Smith O, Bond J, Roberts I, Stam RW, Crump NT, Davies JOJ, Roy A, Milne TAet al., 2025,

  Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression in patients

  , BLOOD, Vol: 146, Pages: 2073-2087, ISSN: 0006-4971
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  • Citations: 1
• Journal article
  Cross JW, Field L, Smith A, Neil E, Hamer L, Jackson T, Elliott N, Rice S, Crump N, Harman J, Ling RE, Wu Q, El Ouazzani N, Thomas R, Inglott S, Bartram J, Smith O, Bond J, Roberts I, Milne TA, Roy Aet al., 2025,

  PROM1/CD133 marks a proliferative stem cell-like population of blasts in KMT2A rearranged infant ALL

  , Blood Advances, Vol: 9, Pages: 4607-4613, ISSN: 2473-9537
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