Activities
- Carry out quality research in the field of haematology and cancer: leukaemia, stem cells, thalassemia and breast cancer.
- Provide diagnostic services: chromosome analysis, DNA analysis and haemoglobin analysis.
- Provide continuous training to the staff in their required field.
Diagnostic Research
The Unit activities are divided into two parts:
1. Haemato-Oncology
- Chromosome Analysis
- Leukaemia Mutation
- Acute Myeloid Leukaemia Mutation
- Chimerism
2. Genetics
- Thalassaemia
- Genetic Disorder Diseases
- Haemophilia B
Research and Development
- Acute Myeloid Leukaemia (AML)
- Lymphoma
- Chronic Myeloid Leukaemia (CML)
- Childhood Leukaemia
- Multiple Myeloma
- Acute Lymphoblastic Leukaemia (ALL)
- Chronic Lymphocytic Leukaemia (CLL)
- Brain Tumor
- Stem Cell
- Induced Pluripotent Stem Cell (iPSC)
- Mesenchymal Stem Cell (MSC)
- Cancer Stem Cell
- Stem Cell Therapy
Research
Genome-Wide Array Comparative Genomic Hybridization Analysis on Patients with Unexplained Developmental Delay (DD), Intellectual Disability (ID), Autism Spectrum Disorders (ASD) or Multiple Congenital Anomalies (MCA)
Array Comparative Genomic Hybridization (aCGH) is a technique that offers rapid genome-wide analysis at high resolution. It facilitates the detection of genomic aberrations or submicroscopic chromosomal alterations at multiple loci simultaneously, which may aid in explaining the causes of several unexplained genetic defects (DD / ID / ASD or MCA) in newborns and children. In Malaysia, many of the referred cases of patients with syndromic features have come out with normal karyotypes, hence a more sensitive method is needed to identify any possible submicroscopic chromosomal aberrations. In this project, we characterised a group of one hundred chromosomally normal patients with unexplained syndromic features via Agilent’s 244K oligonucleotide aCGH platform. Among the 100 patients, 49 (49%) were identified to have unique microdeletion and/or microduplication on their chromosome(s) with aberration sizes ranging from 1.0 to 7.5 Mbp. Using this method, at least 30 genes have been identified to be associated with known syndrome. In conclusion, the aCGH technology offers clinical geneticists a powerful new tool for genome wide screening, with detection of many previously unidentified chromosomal changes now possible. This study has opened up the potential to further identify genes involved in the pathogenesis of such syndromic conditions and confer important implications in genetic counseling and the quality of patient health care in future (Zubaidah Z, Azli I, Fadly MMA, Thong MK, Zarina AL, Keng WT, Choy YS, Ten SK, Puteri JNMB).
Genome-Wide Array Analysis of Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML) Based on Malaysian Genetic Profiles
Leukaemia is a type of cancer characterised by the proliferation of abnormal haemopoietic cells in the bone marrow. In Malaysia, there are high referral numbers of cases where patients with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) being forwarded to our government hospitals. Since most of their karyotypes are normal and any possible chromosomal microaberrations remain undetected using current practices (such as FISH), we applied genome-wide high-resolution Array Comparative Genomic Hybridization (aCGH) technology to assist us in explaining the causes of this cancer. In this study, we characterized a Malaysian cohort of 170 chromosomally-normal acute leukemia cases involving 85 ALL and 85 AML samples via aCGH. Among all of these patients, almost 50% were identified to have unique microdeletion and/or microduplication on their chromosome(s) with aberration sizes ranging from 0.5 to 100.0 Mbp. Using this method, various loci which encoded either single gene, multiple genes or gene-rich regions have been identified and several aberrations overlap with known leukaemic genes in public databases. For the rest of 50% of cases that showed normal results, arrangements of copy number variations (CNVs) throughout their genomes have raised our concern on their involvement in the pathogenesis of the diseases ((Azli I, Puteri JNB, Nor Asiah M, Zubaidah Z).
Figure 1: Microarray scanner for aCGH analysis
Figure 2: Chromosome and gene view of 580 kbp microduplication in 1p36, as detected by aCGH
The quantitative assessment of chimerism : A prospective study in post haematopoietic stem cell transplantation patients.
Haematopoietic chimerism is a measure of the number of donor and recipient cells in the host following haematopoietic stem cell transplantation (HSCT). The aim of this prospective study is to determine the chimeric status in children who underwent HSCT and also to determine whether early chimerism could be detected in post HSCT patients. In this study, two methods will be used to detect chimerism which are the real-time quantitative polymerase chain reaction (PCR) method and the PCR based amplification of the short tandem repeats (STRs)-fragment analysis method. Blood samples from 30 and 27 patients were collected in year 2011 and 2012 respectively and DNA extraction have been done. Genotyping, standard curve amplification and relative quantification were performed for 57 patients using LightCycler 480 (ROCHE) real-time PCR instrument. STR-PCR were also performed for 57 patients using the ABI 3730 DNA Analyzer. This is still an on-going project. (Kueh BL, Rahimah A, Ezalia E, Hishamshah I, Mustaffa H).
Diagnostic Services:
Chimerism Analysis
Chimerism analysis is an important tool to assess the origin of lymphohaematopoietic cells after transplantation. It is important method in predicting disease recurrence, graft versus host disease (GVHD), graft failure or rejection, intercurrent infections and disease relapse. To differentiate factors that influence the outcome of transplantation necessitates post-transplantation follow up of the state of chimerism. We offer this specialized diagnostic service for the evaluation of the state of chimerism after transplantation using either short tandem repeats (STR)-PCR or real-time qPCR methods.
Figure 3: Real-time PCR instrument (LIGHTCYCLER 480, ROCHE)
