Kamariah Ibrahim

Li–Fraumeni syndrome in a Malaysian kindred

We report on a Malaysian kindred with Li-Fraumeni syndrome. The proband was an 8-year-old girl who presented with embryonal rhabdomyosarcoma of the trunk at the age of 8 months and developed a brain recurrence at the age of 7 years, which was 5 years after remission. A younger sister later developed adrenocortical carcinoma at the age of 6 months. Their mother and maternal grandmother were diagnosed with breast cancer at the ages of 26 and 38 years, respectively. TP53 mutation detection in this family revealed a duplication of a GGCGTG motif starting at nucleotide 17579 in exon 10, resulting in an in-frame insertion of two amino acids between residues 334 and 336 in the tetramerization domain of the p53 protein. This mutation was found in the proband and her affected sister as well as her mother. In addition, the mutation was detected in two other siblings (a brother aged 3 years and a sister aged 18 months) who have not yet developed any malignancy. Sequencing of TP53 in the father and two other asymptomatic siblings revealed wild-type TP53. To our knowledge, this is a first report of a Li-Fraumeni syndrome family in Southeast Asia.

Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging

Large epidemiologic studies have reported the premature onset of age‐related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation.

Development of an algorithm of satellite markers for monitoring chimerism status in post-allogeneic haematopoietic stem cell transplantation patients.

Introduction:  Analysis of variable number tandem repeats (VNTRs) by polymerase chain reaction (PCR) is a common method used to predict engraftment status in post‐allogeneic haematopoeitic stem cell transplantation (HSCT) patients. Different populations have different copies of repeated DNA sequence and hence, different percentage of informativeness between patient and donor.

GATA1 mutations in patients with down syndrome and acute megakaryoblastic leukaemia do not always confer a good prognosis.

Children with Down syndrome and acute megakaryoblastic leukemia (DS‐AMKL) have been shown to have increased sensitivity to cytarabine based chemotherapy. The excellent prognosis in patients with DS‐AMKL may be due to mutations in the GATA1 gene leading to reduced expression of the enzyme cytidine deaminase. This leads to a decreased ability to convert cytarabine into its inactive metabolite, resulting in high intracellular concentration of this cytotoxic agent. We report two cases of DS‐AMKL with GATA1 mutations who had poor outcome. These patients had high expression levels of cytidine deaminase mRNA transcripts. We speculate that other factors can affect overall outcome in patients with DS‐AMKL irrespective of the presence of GATA1 mutations. Pediatr Blood Cancer 2009;53:108–111.

Nonclonal Chromosomal Aberrations in Childhood Leukemia Survivors

Abstract Background: Survivors of childhood cancer are at risk of developing a second malignancy. One possible mechanism for neoplastic transformation of cells is through induction of persistent genomic instability. This study aims to seek evidence of chromosomal instability in long-term childhood leukemia survivors (CLS) in one of the largest pediatric academic oncology centers in South East Asia. Methods: 50 asymptomatic (subjects have remained leukemia-free since treatment cessation) CLS and 50 healthy controls were recruited in this cross-sectional study. Of 50 CLS, 44 had acute lymphoblastic leukemia and 6 had acute myeloid leukemia. G-banded karyotyping was performed on unstimulated peripheral blood leukocytes of all subjects. Results: CLS had significantly higher occurrence of karyotypic abnormalities compared to controls. Five CLS harbored six nonclonal abnormalities (mostly aneuploidy) while none were found in controls. Conclusion: Subpopulations with nonclonal chromosomal aberrations were present in peripheral blood leukocytes of our cohort of childhood leukemia long-term survivors.