Dinámica clonal en las neoplasias mieloproliferativas crónicas
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Document Type
Document Version
Author
Director
Bellosillo Paricio, Beatriz
Besses Raebel, C. (Carles)
Besses Raebel, C. (Carles)
Tutor
Other authors
Publication Date
Pages
148 p.
Embargo date
Citation
Fernández Ibarrondo, L. Dinámica clonal en las neoplasias mieloproliferativas crónicas. Universitat Pompeu Fabra; 2024. handle: http://hdl.handle.net/10803/690598
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Citation
Doctoral program
Programa de Doctorat en Biomedicina
Abstract
Las neoplasias mieloproliferativas Philadelphia-negativas son enfermedades clonales que se originan en las células madre hematopoyéticas, ocasionadas por la adquisición de mutaciones driver que afectan a la vía JAK/STAT. Este grupo de enfermedades presentan frecuentemente mutaciones adicionales en genes non-driver. La existencia y la dinámica clonal de los genes driver y non-driver puede influir en el diagnóstico y pronóstico de los pacientes; sin embargo, se desconoce si la exposición a largo plazo con tratamiento citorreductor puede influir en la adquisición de mutaciones en genes non-driver y/o su modulación y aumentar el riesgo de transformación mielofibrótica o leucémica, así como la posibilidad de alcanzar respuesta clinicohematológica y molecular. El objetivo principal de los estudios presentados en esta tesis es analizar la dinámica clonal y modulación de los genes non-driver por el tratamiento citorreductor en pacientes con neoplasias mieloproliferativas Philadelphia-negativas con mutaciones driver en JAK2V617F y en MPL. Adicionalmente, se evalúan las diferencias en el perfil mutacional entre el grupo de pacientes con estas características y pacientes sin tratamiento citorreductor y un grupo control de individuos sanos.
Philadelphia-negative myeloproliferative neoplasms are clonal disorders originated in hematopoietic stem cells, led by the acquisition of driver mutations which affect the JAK/STAT pathway. This group of disease often harbour somatic mutations in non-driver genes. The existence and clonal dynamics of driver and non-driver genes could influence in the diagnosis and prognosis of patients; however, it is unknown whether long-term treatment with cytoreductive therapy could promote de acquisition of non-driver mutations and/or modulate them and if this modification could increase the risk of myelofibrotic or leukemic transformation, as well as the possibility of achieve clinicohematological and molecular response. The main goal of the projects presented in this thesis is to analyze the clonal dynamics and modulation of non- driver genes in patients with Philadelphia-negative myeloproliferative neoplasms with JAK2V617F and MPL driver mutations treated with cytoreductive therapy. Additionally, differences in the mutational profile between the group of patients with these characteristics and patients without cytoreductive treatment and a control group of healthy individuals are evaluated.
Philadelphia-negative myeloproliferative neoplasms are clonal disorders originated in hematopoietic stem cells, led by the acquisition of driver mutations which affect the JAK/STAT pathway. This group of disease often harbour somatic mutations in non-driver genes. The existence and clonal dynamics of driver and non-driver genes could influence in the diagnosis and prognosis of patients; however, it is unknown whether long-term treatment with cytoreductive therapy could promote de acquisition of non-driver mutations and/or modulate them and if this modification could increase the risk of myelofibrotic or leukemic transformation, as well as the possibility of achieve clinicohematological and molecular response. The main goal of the projects presented in this thesis is to analyze the clonal dynamics and modulation of non- driver genes in patients with Philadelphia-negative myeloproliferative neoplasms with JAK2V617F and MPL driver mutations treated with cytoreductive therapy. Additionally, differences in the mutational profile between the group of patients with these characteristics and patients without cytoreductive treatment and a control group of healthy individuals are evaluated.
Keywords
Neoplasias mieloproliferativas, Hidroxiurea, Dinámica clonal, Mutaciones non-driver, Secuenciación masiva, Myeloproliferative neoplasms, Hydroxyurea, Clonal dynamics, Non-driver mutations, Next Generation Sequencing
Subjects
616.4 - Pathology of the lymphatic system, hematopoietic organs, endocrine organs
Publisher
Universitat Pompeu Fabra
