Professor Ursula Kees

Australian Study of Causes of Acute Lymphoblastic Leukaemia in Children

Analysing data collected between 2003 and 2007 in this national case-control study of the risk factors for childhood acute lymphoblastic leukaemia (ALL).

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required.

Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.

The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution

The bone marrow microenvironment plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.

Incidence of NUT carcinoma in Western Australia from 1989 to 2014: a review of pediatric and adolescent cases from Perth Children’s Hospital

NUT carcinoma (NC), previously known as NUT midline carcinoma, is a rare and very aggressive cancer that occurs in both children and adults. NC is largely chemoresistant, with an overall survival of less than 7 months. Because the carcinoma is not restricted to a particular organ, diagnosis is often a challenge. In the absence of a clearly determined incidence for NC, we sought to study the diagnosis of patients in a well-defined population.

Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.

Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin

The prognosis for high-risk childhood acute leukaemias remains dismal and established treatment protocols often cause long-term side effects in survivors. This study aims to identify more effective and safer therapeutics for these patients.

The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution

The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression.

Effective targeting of NAMPT in patient-derived xenograft models of high-risk pediatric acute lymphoblastic leukemia

Our study provides evidence that OT-82 is a promising new therapeutic strategy for a broad spectrum of high-risk pediatric acute lymphoblastic leukemia

Potent antileukemic activity of curaxin CBL0137 against MLL-rearranged leukemia

The aim of our study was to investigate whether CBL0137 has potential as a therapeutic and chemopotentiating compound in MLL-r leukemia

Romidepsin enhances the efficacy of cytarabine in vivo, revealing HDAC inhibition as a therapeutic strategy for KMT2A-rearranged acute lymphoblastic leukemia

In this study, we investigate the in vivo synergy between romidepsin and cytarabine

novel small molecule that kills a subset of MLL-rearranged leukemia cells by inducing mitochondrial dysfunction

This study thus identified a novel small molecule that rapidly kills MLL-rearranged leukemia cells by targeting a metabolic vulnerability

New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment

We provide evidence that targeting leukemia-induced bone loss is a therapeutic strategy for pre-B ALL

Molecular-genetic profiling and high-throughput in vitro drug screening in NUT midline carcinoma-An aggressive and fatal disease

Our data emphasize the heterogeneity of NMC and highlights genetic aberrations that could be explored to improve therapeutic strategies.

Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

Identified romidepsin as a promising therapeutic for mixed lineage leukemia (MLL)-rearranged infant acute lymphoblastic leukemia

Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL

GATA3low ETP-ALL is a novel stem cell-like leukemia with implications for the use of myeloid-derived therapies

High expression of connective tissue growth factor accelerates dissemination of leukaemia

Functional role of CTGF in altering disease progression in a lymphoid malignancy

Heterogeneity in mechanisms of emergent resistance in pediatric T-cell acute lymphoblastic leukemia

Biological changes associated with T-ALL relapse and resistance are stochastic and highly individual

CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements

Identified CCI-007 as a novel small molecule that displays rapid toxicity towards a subset of MLL-r, CALM-AF10 and SET-NUP214 leukemia cell lines

Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

Present a valuable resource for drug discovery and have identified ROM as a promising therapeutic for MLL-rearranged iALL

A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma

In this study, we report the case of an adolescent NMC patient presenting with severe facial pain, proptosis and visual impairment due to a mass arising from...

Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

Connective tissue growth factor (CTGF/CCN2) has been shown previously to be aberrantly expressed in a high proportion of paediatric precursor B cell acute...

The role of CCN family genes in haematological malignancies

Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are...

Rare childhood cancers—an increasing entity requiring the need for global consensus and collaboration

Rare childhood cancers have not benefited to the same extent from the gains that have been made for their frequently occurring counterparts.

Effective targeting of the P53-MDM2 axis in preclinical models of infant MLL-rearranged acute lymphoblastic leukemia.

This study describes the development and molecular characterization of a panel of patient-derived infant leukemia oncogene xenografts and their sensitivity...

Aberrant expression of aldehyde dehydrogenase 1A (ALDH1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T-lineage tumours

The class 1A aldehyde dehydrogenase (ALDH1A) subfamily of genes encode enzymes that function at the apex of the retinoic acid (RA) signalling pathway.

Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality.

Germ-line and somatic DICER1 mutations in pineoblastoma

This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility...

A pre-clinical model of resistance to induction therapy in pediatric acute lymphoblastic leukemia

Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem.

Deregulated expression of connective tissue growth factor is linked to poor outcome in human cancer

Connective tissue growth factor (CTGF/CCN2) has long been associated with human cancers. The role it plays in these neoplasms is diverse and tumour specific.

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell...

The evolution of clinical trials for infant acute lymphoblastic leukemia

Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has...

Comparative drug screening in NUT midline carcinoma

The NUT midline carcinoma (NMC) is a rare but fatal cancer for which systematic testing of therapy options has never been performed.

Bioenergetic modulation overcomes glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia

Drug-resistant forms of acute lymphoblastic leukaemia (ALL) are a leading cause of death from disease in children.

Hypomethylation of the CTGF gene locus is a common feature of paediatric pre-B acute lymphoblastic leukaemia

We identified consistent hypomethylation of the CTGF locus in primary pre-B ALL specimens regardless of CTGF expression.

Drug-gene modeling in pediatric T-cell acute lymphoblastic leukemia highlights importance of 6-mercaptopurine for outcome

This study advances our understanding of drug resistance in T-ALL and provides new markers for patient stratification.

Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline carcinoma

This study contributes to our understanding of the genetic diversity of NMC, an important step towards finding therapeutic targets for a disease that is...

Molecular characterization of identical, novel MLL-EPS15 translocation and individual genomic

Acute Lymphoblastic Leukemia (ALL) occurring in the first year of life is rare.

Fusionfinder: A software tool to identify expressed gene fusion candidates from RNA-seq data

The hallmarks of many haematological malignancies and solid tumours are chromosomal translocations, which may lead to gene fusions.

Interactions between acute lymphoblastic leukemia and bone marrow stromal cells influence response to therapy

To identify links between drug resistance and gene deregulation we used oligonucleotide microarray technology.

MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63

We hypothesized that reactivation of p53 by inhibition of its negative regulator will result in p53-mediated growth arrest and apoptosis.

Pre-natal, clonal origin of t(1;11)(p32;q23) acute lymphoblastic leukemia in monozygotic twins

Investigation of this rare mixed lineage leukemia cytogenetic abnormality aims to provide further evidence of the genetic changes that underpin this leukemia.

Interactions between acute lymphoblastic leukemia and bone marrow stromal cells influence response to therapy

The cure rate for pediatric patients with B precursor acute lymphoblastic leukemia (pre-B ALL) is steadily improving, however relapses do occur despite...

Novel non-TCR chromosome translocations t(3;11)(q25;p13) and t(X;11)(q25;p13) activating LMO2

In T-cell acute lymphoblastic leukemia (T-ALL) cytogenetic alterations juxtapose the LIM-domain-only-2 gene (LMO2) with T-cell receptor loci.

Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia

Rearrangement of the mixed-lineage leukemia gene (MLL) is found in 80% of infant acute lymphoblastic leukemia (ALL) and is associated with poor prognosis and re

Silencing of TESTIN by dense biallelic promoter methylation

Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia and has the potential to contribute to its onset and outcome

Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study

Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive...

Effective adenovirus-mediated gene transfer into neural stem cells derived from human embryonic stem cells

Human embryonic stem cell-derived neural stem cells (hESC-NSCs) are an attractive cell type for studying

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms.

MEIS proteins as partners of the TLX1/HOX11 oncoprotein

Aberrant expression of the TLX1/HOX11 proto-oncogene is associated with a significant subset of T-cell acute lymphoblastic leukemias...

Glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia is associated with a proliferative metabolism

We examined the baseline profile of a panel of T-ALL cell lines to determine factors that contribute to GC resistance without prior drug selection.

Receptor mutation is not a common mechanism of naturally occurring glucocorticoid resistance in leukaemia cell lines

Glucocorticoids (GCs) are among the most important drugs for the treatment of acute lymphoblastic leukaemia (ALL).