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Title: Chromosome 6q16-21 deletions in acute lymphoblastic leukaemia
Author: Sorour, Amani Fouad Abdel Halim
ISNI:       0000 0001 3471 9994
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2002
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The identification of chromosomal abnormalities in acute leukaemia has become an important prognostic parameter for the evaluation of outcome both in adult and childhood patients. However, the prognostic role of some abnormalities, such as deletion of 6q remains to be proven. The aim of the work described in this thesis was threefold. First, to define the region of minimal deletion (RMD) on chromosome 6, band q16-21, deleted, as by cytogenetics analysis, in 5-13% of patients with acute lymphoblastic leukaemia (ALL). Second, to evaluate the incidence of 6q deletion in a homogenous group of adult and childhood ALL patients. Third, to investigate the prognostic value of 6q deletion in a homogenously treated group of patients. Genetic mapping and loss of heterozygosity (LOH) analysis were used to expand from our preliminary data. We used highly informative polymorphic microsatellite markers which are available centromeric and telomeric to 6q21 on 69 paired tumour and remission DNA samples from patients with ALL (34 adults and 35 children). A panel of five microsatellite markers recommended by the national cancer institute (NCI) was also applied to further assess microsatellite instability (MSI). Wild type (WT) was detected in 44 (64%) patients; LOH was demonstrated in 16 (23%) patients and (MSI) was detected in 9 (13%) patients. Our study showed that a RMD is identified by marker D6S1709 on the centromeric side and marker D6S278 on the telomeric side with markers D6S283 and D6S1592 being the most frequently deleted markers. This is to date a region of approximately 3.9MB. Our RMD overlaps with the RMDs previously detected by cytogenetics and fluorescence in situ hybridisation (FISH) analysis. The occurrence of LOH did not appear to segregate with gender, age and immunophenotype or influence clinical outcome in the cohort of patients studied. MSI, however, occurred more frequently in children (17%) than adults (8.8%) but equal frequency was observed in B and T-lineage ALL. Adults with MSI pattern were older than adults with either wild type or LOH pattern. Overall survival was not influenced by the occurrence of either LOH or MSI in B-ALL but conferred worse prognosis in T- ALL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available