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Title: Investigation of clonality and minimal residual disease in haematological malignancy using fluorescent in situ hybridization
Author: Kasprzyk, Arkadiusz
ISNI:       0000 0001 3595 3571
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1998
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Cytogenetic analysis of the malignant clone is clinically important in haematological malignancy. Analysis by metaphase cytogenetics is restricted to the small proportion of malignant cells which are actively dividing. This thesis explores the dynamics of malignant clones using the technique of fluorescence in situ hybridization (FISH) to visualize chromosomal abnormalities in interphase (non-dividing) cells. Hyperdiploid (>46 chromosomes) clones have been investigated by interphase FISH in acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) using appropriate chromosome-specific probes. A hyperdiploid clone was detected in interphase cells in 9/65 patients with ALL in whom metaphase cytogenetics had failed or was normal. A single hyperdiploid cell was identified as clonal in one patient with MDS but not in six others with AML, MDS or ALL. The involvement of different cell lineages in the malignant clone was investigated by simultaneous FISH and identification of the cell type by morphology or monoclonal antibodies. In ALL, hyperdiploid clones were restricted to the lymphoid blasts in 9/9 cases, while Philadelphia (Ph) positive clones, (identified by probes to the genes m- BCR or M-BCR and ABL which fuse as a result of the translocation) were found either in lymphoid blasts alone (1/3 cases) or in both lymphoid and myeloid cells (2/3 cases). In AML trisomy 8 (using a chromosome 8-specific probe) and an 11q23 abnormality (which split YAC 13HH4) were both found only in the myeloid blasts, in 3/3 and 2/2 cases respectively. A sensitive method for the detection of hyperdiploid \geq 50 clones in ALL was developed for minimal residual disease detection. Simultaneous probing of three chromosomes enabled detection of one hyperdiploid cell in 10,000. Heterogeneity in the speed with which the clone was eliminated in remission was seen in 16 patients and early relapse was detected in one patient.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cytogenetic analysis; Malignant clone