WAIMR - Leukemia and Blood Disorders

Leukaemia and Blood Disorders

This group studies genes able to regulate blood cell production, which when mutated cause leukemias. The process of erythropoiesis (formation of red blood cells) is of particular interest to this group, which also examines the molecular mechanism of lineage switching, a phenomenon observed in several leukemias whereby the leukemias suddenly switch from one type to another. The cell line, J2E, which responds to the hormone erythropoietin (Epo), provides an attractive model for studying erythroleukemia, as well as the biochemical and molecular effects of Epo. Recently we have shown that the signalling molecule Lyn is important for the ability of erythroid cells to differentiate, as are a number of interacting molecules.

Whilst J2E cells appear to be "committed" to the red blood cell lineage and do not express any features of other cell types, when they are cultured under adverse conditions, some cells occasionally emerged which displayed characteristics of myeloid (white) cells. These observations showed that cells in one lineage were able to change and enter another pathway. This laboratory identified 2 genes that are differentially expressed between the J2E erythroid cell line and its myeloid derivatives. One of these genes MLF1 is associated with acute myeloid leukemias, while another gene (HLS 5) is a tumour suppressor gene. This group aims to decipher the normal role of these molecules, and how they cause leukemias and cancers when dysregulated.

Senior Research Staff

Professor Peter Klinken

Director, WAIMR

Research: leukaemia and blood disorders; haemopoiesis; erythropoiesis

Dr Robin Scaife

Fellow

Research: cytoskeletal regulation of proliferation and morphological differentiation; gene regulation by nuclear bodies

Dr Louise Winteringham

Fellow

Research: haemopoietic commitment and differentiation; molecules affecting the development of leukemia

Research Details

HLS5

Professor Klinken and his team's discovery of a tumour suppressor gene called HLS5 is providing fresh hope of tackling a number of cancers.

The gene may be able to be used to slow the rate of some cancers. In effect, HLS5 acts in much the same way as a brake cable in a car - if the cable is cut, then the gene can't do its job and cell growth can't be controlled, leading to cancer.

The research could lead to the development of a drug that mimics HLS5 to slow and even stop the growth of cancer cells. The team is also working to produce a test for the gene which could indicate a person's risk of developing breast, prostate, liver, ovarian and colon cancer.

This research has been possible thanks to the support of the WA-based biotechnology company, BioPharmica.

MLF1

Professor Klinken leads WAIMR's Laboratory for Cancer Medicine which has discovered that a gene, called MLF1, is involved in acute myeloid leukaemia, and that it can act to limit treatment of the cancer.

The researchers have discovered the gene is responsible for changes that occur in some leukaemic cells - changes that make them more resistant to chemotherapy and therefore harder to destroy. The finding could open the door to better treatments, with researchers now investigating how they might be able to control the MLF1 gene.

Each year, around 650 Australians are diagnosed with acute myeloid leukaemia and the genetic causes of these leukaemias are gradually being identified. The aggressive cancer, which affects the development of mature blood cells in bone marrow, usually occurs in adults, but can also be diagnosed in children and teenagers.

Notable Achievements