Auner Lab


Dr Holger Auner

  • CRUK Advanced Clinician Scientist
  • Clinical Reader in Molecular Haemato-Oncology

+44 (0)20 3313 4017

Areas of research

Proteotoxic stress and metabolism

Myeloma cells are characterised by a unique sensitivity to inhibitors of the proteasome, which is responsible for the controlled degradation of most cellular proteins that have become damaged or are otherwise unwanted. Nevertheless, resistance to proteasome inhibitors occurs in essentially all patients to varying degrees. Accumulation of misfolded proteins in the endoplasmic reticulum (ER), which triggers proteotoxic ‘ER stress’, is widely believed to be the main mechanism of action of proteasome inhibitors. However, data from our lab and other research groups suggest complex interactions between proteasomal protein degradation and multiple metabolic processes. Our aim is to find metabolic and proteostatic vulnerabilities that we can exploit therapeutically.

Tissue biophysics in myeloma biology

Several important aspects of cancer cell biology are influenced by mechanical cues from the surrounding tissue. In particular, mechanical interactions and matrix remodelling have been shown to govern cancer cell metabolism. Tissue stiffness also impacts on normal haematopoiesis, and mechanical cues are known to modulate therapeutic responses. Moreover, we have shown that proteostasis-targeting drugs can alter tissue physical properties. We aim to understand how tissue stiffness and nutrient availability act together to rewire metabolic networks and regulate drug responses in myeloma.


BibTex format

author = {Auner, HW and Iacobelli, S and Sbianchi, G and Knol-Bout, C and Blaise, D and Russell, NH and Apperley, JF and Pohlreich, D and Browne, P and Kobbe, G and Isaksson, C and Lenhoff, S and Scheid, C and Touzeau, C and Jantunen, E and Anagnostopoulos, A and Yakoub-Agha, I and Tanase, A and Schaap, N and Wiktor-Jedrzejczak, W and Krejci, M and Schönland, SO and Morris, C and Garderet, L and Kröger, N},
doi = {10.3324/haematol.2017.181339},
journal = {Haematologica},
pages = {514--521},
title = {Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party},
url = {},
volume = {103},
year = {2017}

RIS format (EndNote, RefMan)

AB - Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972).
AU - Auner,HW
AU - Iacobelli,S
AU - Sbianchi,G
AU - Knol-Bout,C
AU - Blaise,D
AU - Russell,NH
AU - Apperley,JF
AU - Pohlreich,D
AU - Browne,P
AU - Kobbe,G
AU - Isaksson,C
AU - Lenhoff,S
AU - Scheid,C
AU - Touzeau,C
AU - Jantunen,E
AU - Anagnostopoulos,A
AU - Yakoub-Agha,I
AU - Tanase,A
AU - Schaap,N
AU - Wiktor-Jedrzejczak,W
AU - Krejci,M
AU - Schönland,SO
AU - Morris,C
AU - Garderet,L
AU - Kröger,N
DO - 10.3324/haematol.2017.181339
EP - 521
PY - 2017///
SN - 0390-6078
SP - 514
TI - Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party
T2 - Haematologica
UR -
UR -
VL - 103
ER -