Myeloma Research Laboratory

Myeloma Research Laboratory

Here at the Myeloma Research Laboratory we study the molecular and cellular basis for the development of the bone marrow cancer, multiple myeloma (MM). Myeloma is characterised by the clonal proliferation of malignant plasma cells (an immune cell type that normally protects us against infection).

Myeloma is the second most common blood cancer affecting humans, with over 1,500 Australians diagnosed each year. Despite recent advances in treatment, myeloma remains almost universally fatal with a 10 year survival rate of approximately 17%.

The main clinical manifestations of myeloma are the development of osteolytic bone lesions, bone pain, hypercalcaemia, renal insufficiency, suppressed immunoglobulin production and increased BM angiogenesis (blood vessel formation).

It is now widely accepted that most, if not all, cases of myeloma are preceded by a premalignant (asymptomatic) monoclonal gammopathy of uncertain significance (MGUS) stage. However, the genetic factors which trigger the progression from this asymptomatic stage of the disease to overt malignant myeloma remain to be determined. Moreover, recent studies suggest that the bone marrow microenvironment plays a central role in disease progression.

Our laboratory’s research is focussed on identifying the key genes which are responsible for disease progression and the role played by the bone microenvirnment in disase pathogenesis. We believe that these approaches will enable us to identify new molecular markers of disease risk and to design drugs against novel therapeutic targets.

Current research

Current projects are focused on:

  • Identification of genetic factors which trigger the progression from asymptomatic MGUS to overt malignant MM.
  • Defining the role of the bone marrow microenvironment in the development MM.
  • Determining the effects of myeloma plasma cells on mesenchymal stem cell differentiation.
  • Identifying the role of the mTOR pathway in mesenchymal stem cell biology and bone formation.

Read more about our current research.

Recent publications

Psaltis PJ, Paton S, See F, Arthur A, Martin S, Itescu S, Worthley SG, Gronthos S, Zannettino AC. Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations. J Cell Physiol. 2010 May;223(2):530-40.

Winkler IG, Barbier V, Wadley R, Zannettino AC, Williams S, Lévesque JP. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct non-perfused niches. Blood. 2010 Apr 14. [Epub ahead of print]

Williams SA, Martin SK, Vincent C, Gronthos S, Zheng T, Atkins GJ, Zannettino AC. Circulating levels of TWEAK correlate with bone erosion in multiple myeloma patients. Br J Haematol. 2010 Apr 12.

Engler JR, Frede A, Saunders VA, Zannettino AC, Hughes TP, White DL. Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity. Leukemia. 2010 Apr;24(4):765-70. Epub 2010 Feb 11. [IF = 8.634; CN = 0].

Vandyke K, Dewar AL, Diamond P, Fitter S, Schultz CG, Sims NA, Zannettino AC.  The tyrosine kinase inhibitor dasatinib dysregulates bone remodelling through inhibition of osteoclasts in vivo. J Bone Miner Res. 2010 Mar 11. [Epub ahead of  print].