Research Projects
The Asian Myelodysplastic Syndrome (MDS) and Secondary Acute Myeloid Leukaemia (AML) Project


Programme(s) to which this project applies:
☒ MPhil/PhD ☑ MRes[Med] ☒ URIS

Objective and Significance:

Myelodysplastic syndrome (MDS) is a group of clonal haematopoietic stem cell disorders characterized by ineffective haematopoiesis leading to cytopenia, with a significant risk of progression to acute myeloid leukaemia (AML). Recurrent mutations are found in over 85% of cases. Treatment of high-risk MDS involves the use of hypomethylating agents (HMA), and allogeneic haematopoietic stem cell transplantation (HSCT). Treatment with HMAs achieves response rate of about 40% in high-risk patients, and median duration of response of merely 9 to 15 months. HMA failure is associated with a dismal outcome and a median survival of less than 5 months. Therefore, progression to AML and resistance to HMA are important unmet clinical needs. Early prediction of leukemic progression and HMA resistance might improve outcome by early triage to HSCT. There is currently no well-established model incorporating clinicopathologic and genetic data for predicting leukemic transformation and HMA failure. Furthermore, there is a lack of large multicentre registry of clinical and genetic information in Asian patients with MDS.

Objectives

To establish a prognostic model incorporating clinicopathologic and genetic data for Asian MDS patients, for the prediction of survivals, HMA resistance and leukemic transformation.

Significance

Clinical impacts include

  1. Prognostication based on molecular aberrations supplements current models to stratify patients for optimal treatment
  2. Prediction of HMA resistance
  3. Prediction of leukaemic transformation
  4. Identification of known and novel molecular therapeutic targets

Research Plan and Methodology:

Analysis

Data on clinicopathologic features, cytogenetics, genetic mutation profile, disease progression and treatment outcome will be collected in a retrospective and prospective cohort of 1600 Asian patients with MDS. Mutations will be determined by next-generation sequencing using a myeloid gene panel comprising 69 genes of potential diagnostic, prognostic or therapeutic significance. The sample size of 1600 will establish a prognostic model integrating clinicpathologic, cytogenetic and molecular information.

Infrastructure

Asian Myeloid Working Group (Hong Kong as the lead, Singapore, Taiwan, Thailand, Malaysia, Korea, the Philippines) has been established since May 2017 It is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03169296).

Dr GHH Singh, Department of Medicine

Biography
gillhsh@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

  1. your CV,
  2. a brief description of your research interest and experience, and
  3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information. 

Research @ Department of Medicine