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Investigating Ikaros deletions in cohort of South African acute lymphoblastic leukemia patientsMoodley, Mishalan 22 August 2014 (has links)
INTRODUCTION: Despite best current therapy, acute lymphoblastic leukemia (ALL) still remains the most common cause of cancer-related death in children and young adults. Relapse is the main reason for treatment failure in ALL patients and occurs in 15-20% of these patients. Current risk stratification criteria have not been sufficient to predict relapse in ALL patients. The Philadelphia (Ph) chromosome is a chromosomal abnormality found in a subset of high risk ALL patients and is associated with a poor prognosis. Recent genome-wide studies have identified focal deletions of the Ikaros gene (IKZF1) in 70-80% of B-cell ALL patients that have the Philadelphia (Ph) chromosome. Subsequent studies have also found a strong correlation between IKZF1 deletions and ALL patients (Ph+ and Ph-) that relapse. IKZF1 is required for normal lymphoid development and loss of IKZF1 results in haploidinsufficiency or the overexpression of dominant negative IKZF1 isoforms, in particular Ik6 in high risk ALL patients. Most studies used DNA microarrays to detect IKZF1 deletions. Multiplex ligation probe dependent amplification (MLPA) is a low cost, rapid technique that can detect small DNA copy number changes of up to 50 targets in a single reaction and is not as technically challenging to analyse as arrays. MLPA has also been suggested to be used as an alternative to array based techniques in developing countries. METHODS: There were 31 ALL (paediatric and adult) patients that were tested using MLPA and 24 ALL patients tested using reverse transcriptase PCR (RT-PCR) to detect IKZF1 copy number changes and IKZF1 isoform expression pattern respectively. RT-PCR was validated with DNA sequencing and MLPA was validated with Fluorescent in situ hybridization (FISH). MLPA was also compared to cytogenetics in certain cases. RESULTS: MLPA detected 156 copy number changes (7.1 aberrations per sample) in 22 leukemic patients. IKZF1 deletions accounted for the majority of the aberrations (41%) and were detected in 53% of Ph+ ALL patients (n=15) by MLPA. IKZF1 deletions were detected at presentation and relapse in Ph+ and Ph- ALL patients. IKZF1 isoform Ik6 was detected in 70% of Ph+ and relapsed ALL patients after performing RT-PCR. IKZF1 deletions of exons 4-7 resulted in exclusive expression of Ik6. MLPA results were also correlated with certain aneuploidies detected
with cytogenetics. CONCLUSION: This study showed that IKZF1 deletions could have assisted with prognosis in certain ALL cases and thus, newly diagnosed ALL patients should be screened for IKZF1 deletions. MLPA proved to be a reliable, rapid and cost effective technique to detect small copy number changes in multiple genes and should be implemented as a diagnostic test to detect IKZF1 deletions.
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Regulation of antibody production in immunocompromised patients /Nilsson, Anna, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.
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Acute lymphoblastic leukaemia in adult patients : studies of prognostic factors, treatment results and in vitro cellular drug resistance /Hallböök, Helene, January 2005 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.
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Dental Maturation in Children Treated for Acute Lymphocytic LeukemiaWeathersby, Michael Grey, January 2006 (has links) (PDF)
Thesis (M.S. )--University of Tennessee Health Science Center, 2006. / Title from title page screen (viewed on October 17, 2008). Research advisor: Edward Harris, Ph.D. Document formatted into pages (xxvii, 301 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 133-153).
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Standardization and application of quantitative PCR methods in patients with hematological malignancies /Malec, Maria, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.
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Genetic studies of acute lymphoblastic leukemia /Kuchinskaya, Ekaterina, January 2007 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.
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Multiparameter flow cytometry and minimal residual disease in patients with acute leukemia /Björklund, Elisabet, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.
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"Estudo duplo-cego comparativo entre prednisona e dexametasona na avaliação da reserva adrenal em crianças e adolescentes com leucemia linfocítica aguda" / Evaluation of adrenal reserve in children and adolescents with acute lymphocytic leukemia through a double-blind comparison between Prednisone and DexamethasoneHilton Kuperman 30 November 2005 (has links)
Para avaliar a reserva adrenal após o uso de glicocorticóide na fase de indução de remissão em pacientes com Leucemia Linfocítica Aguda, estudo duplo-cego foi realizado em 29 crianças e adolescentes de 1,7 a 15,9 anos (média:6,8 anos], que receberam por escolha aleatória, Prednisona na dose de 40 mg/m²/dia ou Dexametasona, 6 mg/m²/dia, via oral, por um mês. Testes do ACTH em baixa dose (1,0 µg/m² EV) foram realizados antes e a cada 7 dias por 8 semanas para avaliar pico de cortisol após o estímulo. Não houve diferença significativa entre as médias dos picos de cortisol nos testes realizados em cada grupo e entre os dois grupos, mostrando reserva adrenal adequada. Não houve correlação entre os picos de cortisol nos dois grupos e a presença de infecção / In order to evaluate adrenal reserve after adminstration of glucocorticoid during induction phase in patients with Acute LymphociticLeukemia, a double-blind study was performed in 29 children and adolescents 1,7 to 15.9 years old (mean: 6.8 years old), who randomly were chosen to receive either Prednisone, 40 mg/m²/day or Dexamethasone, 6 mg/m²/day, PO, for one month. Low-dose ACTH tests (1.0 µg/m² IV), were performed before and every 7 days after glucocorticoid for 8 weeks. There were no significant differences of cortisol mean peak levels in the tests of each group and in both group, suggesting adequate adrenal reserve. There was no correlation of cortisol mean peak levels in both groups and the presence of infection
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"Estudo duplo-cego comparativo entre prednisona e dexametasona na avaliação da reserva adrenal em crianças e adolescentes com leucemia linfocítica aguda" / Evaluation of adrenal reserve in children and adolescents with acute lymphocytic leukemia through a double-blind comparison between Prednisone and DexamethasoneKuperman, Hilton 30 November 2005 (has links)
Para avaliar a reserva adrenal após o uso de glicocorticóide na fase de indução de remissão em pacientes com Leucemia Linfocítica Aguda, estudo duplo-cego foi realizado em 29 crianças e adolescentes de 1,7 a 15,9 anos (média:6,8 anos], que receberam por escolha aleatória, Prednisona na dose de 40 mg/m²/dia ou Dexametasona, 6 mg/m²/dia, via oral, por um mês. Testes do ACTH em baixa dose (1,0 µg/m² EV) foram realizados antes e a cada 7 dias por 8 semanas para avaliar pico de cortisol após o estímulo. Não houve diferença significativa entre as médias dos picos de cortisol nos testes realizados em cada grupo e entre os dois grupos, mostrando reserva adrenal adequada. Não houve correlação entre os picos de cortisol nos dois grupos e a presença de infecção / In order to evaluate adrenal reserve after adminstration of glucocorticoid during induction phase in patients with Acute LymphociticLeukemia, a double-blind study was performed in 29 children and adolescents 1,7 to 15.9 years old (mean: 6.8 years old), who randomly were chosen to receive either Prednisone, 40 mg/m²/day or Dexamethasone, 6 mg/m²/day, PO, for one month. Low-dose ACTH tests (1.0 µg/m² IV), were performed before and every 7 days after glucocorticoid for 8 weeks. There were no significant differences of cortisol mean peak levels in the tests of each group and in both group, suggesting adequate adrenal reserve. There was no correlation of cortisol mean peak levels in both groups and the presence of infection
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Cell death mechanisms of anti-cancer agents and treatment response in acute leukemia /Laane, Edward, January 2006 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.
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