Identifying genetic and epigenetic changes underlying pediatric acute myeloid leukemia progression

  • Bensmail, Halima (Lead Principal Investigator)
  • Ahmed, Nisar (Graduate Student)
  • Cugno, Dr.Chiara (Principal Investigator)

Project: Experimental Development/Translation Research

Project Details

Abstract

Leukemia is the most common pediatric cancer in Qatar. Similar to global statistics, it accounts for over 40% of new pediatric cancer cases (QNRC, 2015), therefore it is a national priority to better understand leukemia and develop new methods that aid patient stratification and prognosis. Most pediatric leukemia patients respond well to current treatment regimes, for example Acute Lymphocytic Leukemia (ALL) has close to 90% 5-year overall survival rate. In contrast, Acute Myeloid Leukemia (AML) has a higher relapse rate and much lower (~65%) overall survival rate. It is difficult to predict which patients will relapse, because there are only a few recurrent mutations that are associated with poorer prognosis (e.g. FLT3, WT1). Furthermore, in pediatric cancers it is equally important to identify patients with good prognosis to avoid overtreatment. In order to achieve remission, all AML patients currently receive high doses of chemotherapeutic drugs, such as daunorubicin and cytarabine, which have considerable long-term adverse effects, thereby reducing the quality of life and increasing morbidity and mortality. Better patient stratification is needed to achieve risk-directed optimal intensity and combination of therapy. Here we focus on AML to investigate what causes 35-40% of pediatric AML cases to relapse conferring poor outcome. This project employs a multi-omics approach to elucidate how somatic mutations and long-range regulatory interactions contribute to relapse in pediatric Acute Myeloid Leukemia (AML) patients carrying distinct chromosomal rearrangements. We will access patient samples from the pediatric AML ‘MyeChild’ drug trial in the UK and from the pediatric oncology unit in Sidra. At both locations, there is a working procedure to follow up and collect samples from relapsing patients, to enable study of paired diagnostic and relapse samples. We will answer the following questions: • Do transcriptional and long-range regulatory interaction patterns discriminate pediatric AML subtypes? • Does the regulatory landscape differ in children compared to adults? • What are the changes in gene expression regulation and which regulatory elements are involved in disease progression? • Can we use next generation artificial intelligence methods to learn about features present in diagnosis samples that could predict whether the patient is likely to relapse? This will be the first project that investigates the contribution of regulatory chromatin interactions to cancer progression. Therefore, we are confident that our project will lead to high-impact publications in the fields of cancer biology, epigenetics and computational biology and that the findings will help refine the future directions of AML patient stratification.

Submitting Institute Name

Hamad Bin Khalifa University (HBKU)
Sponsor's Award NumberNPRP13S-0116-200088
Proposal IDEX-QNRF-NPRPS-25
StatusActive
Effective start/end date1/07/2131/01/25

Collaborative partners

Primary Theme

  • Precision Health

Primary Subtheme

  • PH - Preventative health

Secondary Theme

  • Precision Health

Secondary Subtheme

  • PH - Diagnosis Treatment

Keywords

  • Epigenomics
  • Bioinformatics
  • Gene expression regulation

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