Mutation find may help leukaemia patients

Dr Cedric Tremblay (right) with a co-author,
PhD student Dr Sung Kai Chui.  The
research group has identified a cancer
promoting mutation. See paper.

by Anne Crawford

Researchers from Monash University’s Australian Centre for Blood Diseases (ACBD) have become the first scientists to describe the mechanisms by which a recently identified mutation makes leukaemia cells more aggressive. Their work is progressing in preclinical trials that may lead to the development of a drug to help treat patients with T-cell acute lymphoblastic leukaemia (T-ALL) who are resistant to conventional chemotherapy.

Gene mutations in T-cell acute lymphoblastic leukemia (T-ALL)

Image: American Society of Hematology

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of T-cell progenitors, with overall survival rates of 70% in children and <40% in adults. The majority of T-ALL cases harbour activating mutations in NOTCH1, which encodes a membrane-spanning receptor essential for lineage commitment and development of T-lymphocytes. Activating NOTCH1 mutations occur in ~60% of human T-cell acute lymphoblastic leukemias (T-ALLs), and mutations disrupting the transcription factor IKZF1 (IKAROS) occur in ~5% of cases. These results demonstrate for the first time that aberrant NOTCH activity compromises IKAROS function in mouse and human T-ALL, and provide a potential explanation for the relative infrequency of IKAROS gene mutations in human T-ALL.

Reference: Witkowski MT, Cimmino L, Hu Y, Trimarchi T, Tagoh H, McKenzie MD, Best SA, Tuohey L, Willson TA, Nutt SL, Busslinger M, Aifantis I, Smyth GK, Dickins RA. Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia. Leukemia. 2015 Jun;29(6):1301-11. doi: 10.1038/leu.2015.27. Epub 2015 Feb 6.

Damien Easton awarded MCCC travel grant

Congratulations to Damien Easton on receiving the Monash Comprehensive Cancer Consortium (MCCC) travel grant. 

The travel grant is awarded by the Monash Comprehensive Cancer Consortium (MCCC) to fund attendance at the International Keystone Symposium on Tumor Immunology, in Canada in 2015. Damien will be presenting his work on Chronic Lymphocytic Leukemia (CLL) which is the most common leukemia in adults and is currently not curable.

Dr Catherine Carmichael joins ACBD

Dr Catherine Carmichael

Welcome to Dr Catherine Carmichael from the Walter and Eliza Hall Institute (WEHI), whose expertise is on the regulation of both normal and abnormal blood cell development especially in relation to leukaemia. Dr Carmichael received her PhD from the University of Melbourne in 2008, studying genetic predispositions to haematological malignancies. She was a postdoc for 6 years at WEHI studying the role of the ETS-related gene, ERG, during leukaemia development. She has now joined the Australian Centre for Blood Diseases Mammalian Functional Genetics lab of A/Prof Jody Haigh as a Research Fellow, and is studying the role of Epithelial-Mesenchymal Transition (EMT) modulators during both normal blood cell production ("haematopoiesis") and leukaemia development. See more at www.acbd.monash.org/research/mammal-genetics.html

A new role discovered for a familiar enzyme: PI3K and the regulation of cell survival

In recent studies headed by Dr Mark Guthridge in the Leukemia Research Laboratory at the Australian Centre for Blood Diseases, Monash University and published in PLOS Biology, a new role was identified for the protein kinase activity of PI3K in regulating the “survival-only” response of human hematopoietic (blood) cells. These studies provide the first evidence that the protein kinase activity of PI3K can control cell survival and that this activity is a therapeutic target in cancer.

Research: Stem Cell Research Group, Division of Blood Cancers

Lmo2 is an oncogenic transcription factor that is frequently overexpressed in T cell acute lymphoblastic leukemia (T-ALL) including early T-cell precursor ALL (ETP-ALL) cases with poor prognosis. Lmo2 must be recruited to DNA by binding to the hematopoietic basic helix-loop-helix (bHLH) factors Scl/Tal1 or Lyl1. However, it is unknown which of these factors can mediate the leukemic activity of Lmo2.

Researchers discover an Achilles heel of childhood leukaemia

Research led by Associate Professor David Curtis at the Australian Centre for Blood Diseases (ACBD) has identified a protein essential for the development and growth of a type of childhood leukaemia (ETP-ALL) that responds poorly to current treatments.