Retinoblastoma: a recent experience at the National University Hospital, Singapore.

INTRODUCTION: Retinoblastoma is a very rare disease. There were 30 cases of retinoblastoma diagnosed and treated at National University Hospital (NUH). MATERIALS AND METHODS: A retrospective chart review was performed on the medical records of 30 patients who were diagnosed with retinoblastoma between 1995 and 2008 at the Department of Paediatrics, National University Hospital, Singapore. RESULTS: The median age at diagnosis was 1.6 years (range, 0-5.9) with a median follow-up of 1.8 years (range, 0.1 to 11.6). The median time from presenting signs to the time of diagnosis was 5.2 months (range, 0-25.2). Common presenting signs of retinoblastoma were identified; the most common of which were leukocoria (50.0%), squinting (13.3%), poor vision (10.0%), strabismus (6.6%) and unknown (33.3%). Of the 30 patients, 10 were from Singapore whilst the other 20 patients were from the surrounding countries. Twelve patients had bilateral disease at the time of diagnosis, while 18 had unilateral disease. Staging information was available in 27 patients. Enucleation was performed in 25 of 30 patients. Radiation therapy was given in 3 patients in 1995 (bilateral disease), 2001 (bilateral disease) and 2003 (unilateral disease). At the time of analysis, 19 patients were alive with no evidence of disease. Overall 5-year survival for the cohort was 88.1% [95% confidence interval (CI), 88.0-100] and event-free survival for the whole cohort was 74.2% (95% CI, 55.8-92.6). CONCLUSION: In our limited experience, the importance of collaboration and standardisation of the staging system, raising awareness and education of primary healthcare providers and parents are strongly stressed.

Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.

Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the prognostically important leukemia subtypes, including T-ALL, E2A-PBX1, BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes. In addition, another ALL subgroup was identified based on its unique expression profile. Examination of the genes comprising the expression signatures provided important insights into the biology of these leukemia subgroups. Further, within some genetic subgroups, expression profiles identified those patients that would eventually fail therapy. Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients.

Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia.

The AML1/CBFbeta transcription factor complex, a frequent target of chromosomal translocations in leukemia, is essential for the generation of definitive hematopoietic stem cells. Paradoxically, expression of the acute myeloid leukemia-associated AML1-ETO fusion protein in mice results not in leukemia, but in embryonic lethality due to an absence of normal hematopoiesis. To bypass the embryonic lethality, we generated a mouse strain with a conditional AML1-ETO knockin allele that contains a loxP bracketed transcriptional stop cassette 5' to the AML1-ETO fusion site. Activation of this allele in vivo by Cre-mediated recombination resulted in an enhanced replating efficiency of myeloid progenitors, but it did not block their differentiation, nor was it sufficient to induce leukemia. However, induction of cooperating mutations resulted in the development of an acute myeloid disease that mimicked many of the features of human AML1-ETO-expressing leukemia.