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Translational Genomics in Leukaemia

The Translational Genomics in Leukaemia team is focused on identifying the causes of leukaemia, with the goal of developing new targeted treatments to improve quality of care and long-term survival for all children with leukaemia.

It is more “unbalanced” than you think

Sébastien Malinge PhD Laboratory Head, Translational Genomics in Leukaemia, Senior Research Fellow (University of Western Australia), Adjunct Senior

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.

Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia model

Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations.

Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society

Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome.

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.

DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3

DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.

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.

Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome

Structural and numerical alterations of chromosome 21 are extremely common in hematological malignancies. While the functional impact of chimeric transcripts from fused chromosome 21 genes such as TEL-AML1, AML1-ETO, or FUS-ERG have been extensively studied, the role of gain of chromosome 21 remains largely unknown.

Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia

Children with Down syndrome (constitutive trisomy 21) that develop acute lymphoblastic leukemia (DS-ALL) have a 3-fold increased likelihood of treatment-related mortality coupled with a higher cumulative incidence of relapse, compared with other children with B-cell acute lymphoblastic leukemia (B-ALL).

Archive

Years May January October April View the infographics that we have published in 2023 including building a secure attachment with your child, back to

2023

View the infographics that we have published in 2023 including building a secure attachment with your child, back to school anxiety in little kids, playful parenting, and more.

2022

View the infographics that we have published in 2022, including shyness in young children, early diagnosis of mental health disorders in children, nightmares & night terrors, and more.

Prevalence of electronic device use before bed among Australian children and adolescents: a cross-sectional population level study

To understand the prevalence of children and adolescents’ electronic device use (EDU) in the hour before bed and identify sociodemographic groups that are at increased risk of problematic use.

Occurrence of psychosis and bipolar disorder in adults with autism: A systematic review and meta-analysis

Evidence suggests that individuals with autism spectrum disorder have increased rates of co-occurring psychosis and/or bipolar disorder. Considering the peak age of onset for psychosis and bipolar disorder occurs in adulthood, we investigated the co-occurrence of these disorders in adults with autism.

Is ‘a little’ too much?: An exploration of women’s beliefs about alcohol use during pregnancy

Interventions to address alcohol use during pregnancy need to target underlying determinants of the behaviour. Using the theory of planned behaviour as a theoretical framework, the aim of this study was to identify behavioural, normative and control beliefs regarding alcohol use during pregnancy among a sample of women.

A Review of Self-Compassion as an Active Ingredient in the Prevention and Treatment of Anxiety and Depression in Young People

Previous meta-analyses have found higher self-compassion is associated with lower anxiety and depression. The aim of this study was to investigate the efficacy of self-compassion as an active ingredient in the treatment and prevention of anxiety and depression in youth. This was conducted through (i) a systematic review of the literature and (ii) qualitative consultation with young people and researchers in self-compassion.

Self-Compassion, Wellbeing, and Distress in Adolescents and Young Adults with Chronic Medical Conditions: the Mediating Role of Emotion Regulation Difficulties

Adolescents and young adults with chronic medical conditions report higher distress and lower wellbeing than their physically healthy peers. Previous research suggests that self-compassion is negatively correlated with distress and positively correlated with wellbeing among healthy young people, as well as adults with chronic medical conditions.

Caregiver-mediated interventions to support self-regulation among infants and young children (0-5 years): A protocol for a realist review

Self-regulation is a modifiable protective factor for lifespan mental and physical health outcomes. Early caregiver-mediated interventions to promote infant and child regulatory outcomes prevent long-term developmental, emotional and behavioural difficulties and improve outcomes such as school readiness, educational achievement and economic success. To harness the population health promise of these programmes, there is a need for more nuanced understanding of the impact of these interventions.

The oral and written narrative language skills of adolescent students in youth detention and the impact of language disorder

Unmet language and literacy needs are common among young people who are involved with youth justice systems. However, there is limited research regarding the functional text-level language skills of this population with regard to narrative macrostructure (story grammar) and microstructure (semantics and syntax) elements. In this study, we examined macrostructure and microstructure elements in the oral and written narrative texts of 24 adolescent students of a youth detention centre. The students, who were aged 14- to 17- years, were all speakers of Standard Australian English, and 11 (46%) students met criteria for language disorder (LD).