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Fluorescence-in-situ hybridization in adult all cytogenetic findings and clinical correlation.

Al-Obaidi, M.S.J.; (2005) Fluorescence-in-situ hybridization in adult all cytogenetic findings and clinical correlation. Doctoral thesis , University of London. Green open access

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Abstract

Since the first reports of cytogenetic abnormalities in ALL, repeated small and large scale studies have shown that cytogenetic abnormalities detected at presentation continue to be the most important predictor of outcome in ALL, at presentation, on relapse and even in the context of more intensive treatment modalities. The accuracy of diagnosis is much improved by the additional application of molecular techniques including FISH, which is the technique I used to more accurately define the cytogenetic abnormalities in a series of 176 adult patients with ALL. I have studied the incidence of and clinical features associated with three important structural abnormalities, namely BCR/ABL, MLL and ETV6/AML1 abnormalities, as well as alterations in chromosome number and showed that FISH with commercial probes provides a simple and accurate method for the detection of these abnormalities in presentation samples. FISH detected cytogenetically silent abnormalities in twenty-four of the 176 patients. In addition to the patients positive for rearranged genes, I uncovered a rare case of Philadelphia negative BCR/ABL ALL with aberrant insertion ofABL into a morphologically normal chromosome 9q. I went on to study in detail twenty-nine cases with indeterminate cytogenetics, and was able to further characterize the karyotype in fifteen of these. I have shown the applicability of sequential FISH a technique developed in our laboratory, in identifying underlying complex chromosomal abnormalities, even when metaphase number and morphology is very poor. In a number of cases the additional findings appear to influence clinical outcome. Finally by assessing the total cytogenetic information, as well as a number of clinical variables at presentation I developed a simple method of risk stratification for adult patients with ALL which distinguishes three subgroups, including a population accounting for 32% of 159 patients studied who appear to have significantly better outcomes when treated according to the UK ALL XII protocol.

Type: Thesis (Doctoral)
Title: Fluorescence-in-situ hybridization in adult all cytogenetic findings and clinical correlation.
Identifier: PQ ETD:591749
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1444445
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