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Please use this identifier to cite or link to this item: http://hdl.handle.net/10277/547

Authors: Mare, Lydia
Internal Tutor: LO CURTO, FRANCESCO
Title: Array-CGH in the investigation of karyotype changes of CD34+ haematopoietic stem cells in lymphoma and multiple myeloma patients who underwent to autologous transplantation.
Abstract: Hematopoietic stem cell transplantation (HSCT) represents an effective treatment strategy for a variety of hematologic and not hematologic malignancies. In particular, autologous transplantation of haematopoietic stem cells (ASCT) from bone marrow of patients with hematologic malignancies is feasible and has low treatment-related mortality (Gribben JG, 2009). However, literature assessed late mortality in 29.4% of individuals who had survived 2 or more years after autologous haematopoietic cell transplantation (Burns, L.J., 2009; Bhatia S. and al, 2005). This could be due to the purified stem cells which might carry a mutation on a chromosome predisposing to the disease and lead to the risk of pathology recurrence. Lymphoma and myeloma are perfect candidates for autologous transplantation after G-CSF stimulation and bone marrow ablation trough chemotherapy. However, in this case too, pathology relapse or secondary malignancies are found in a high percentage of patients. The aim of this project is to verify the existence of detectable imbalanced chromosome anomalies in stem cells before any ablative treatment for HSCT or developed after G-CSF stimulation or chemotherapy. A cohort of 24 lymphoma and myeloma patients have been analyzed trough array-CGH to identify significant imbalanced chromosome anomalies also present in low percentage of mosaicism. The result showed anomalies in 8/24 patients: one patient affected by Hodgkin Lymphoma (HL) revealed a deletion of chromosome 2 in p16.1, where the REL gene is located and in part deleted; the amplification of chromosome 11 in q12.2q13.4 containing CCND1 gene (this patient was investigated both before and after transplantation) was found in one patient with multiple myeloma (MM); alterations of chromosome 14 in q32.31-33, where genes for variable chain of immune globulin are located, were found in five patients with Hodgkin and non Hodgkin lymphomas (HL/NHL). FISH on interphase nuclei has been used to confirm a-CGH data. A short-time (36 months) clinical and haematological follow-up examination did not show a different trend between patients with chromosome imbalances and without but a long-term follow-up is needed to definitely correlate the imbalances with the clinical evolution and to have the indications of global survival of the considered population. Work in progress is the extension of clinical and haematological observation to obtain evidence of a difference statistically significant and to reach the final goal of suggesting a possible protocol to candidate patients to purging treatments before the CD34+ cells re-infusion.
Keywords: Array-CGH, lymphoma, multiple myeloma, autologous transplantation.
Subject MIUR : MED/03 GENETICA MEDICA
Issue Date: 2014
Language: eng
Doctoral course: Medicina Sperimentale e Oncologia
Academic cycle: 26
Publisher: Università degli Studi dell'Insubria
Citation: Mare, L.Array-CGH in the investigation of karyotype changes of CD34+ haematopoietic stem cells in lymphoma and multiple myeloma patients who underwent to autologous transplantation. (Doctoral Thesis, Università degli Studi dell'Insubria, 2014).

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