Tesi etd-05052025-183540 |
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Tipo di tesi
Tesi di laurea magistrale LM6
Autore
TROMBELLO, LIDIA
URN
etd-05052025-183540
Titolo
Disentangling the Prognostic Landscape of Chronic Myeloid Leukemia: From Epigenetic Regulators to Inflammatory and Immune Markers
Dipartimento
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di studi
MEDICINA E CHIRURGIA
Relatori
relatore Prof.ssa Galimberti, Sara
correlatore Prof.ssa Baldini, Chiara
correlatore Prof.ssa Baldini, Chiara
Parole chiave
- BCR::ABL1
- BMI1
- epigenetica
- epigenetics
- evasione immunitaria. chronic myeloid leukemia
- EZH2
- genetic polymorphisms
- IGFBP6
- immune evasion
- infiammazione
- inflammation
- inibitori delle tirosin-chinasi
- leucemia mieloide cronica
- PD-L1
- polimorfismi genetici
- risposta terapeutica
- ROCK2
- therapeutic response
- tyrosine kinase inhibitors
Data inizio appello
21/05/2025
Consultabilità
Non consultabile
Data di rilascio
21/05/2028
Riassunto
La leucemia mieloide cronica (LMC) è caratterizzata dalla presenza della proteina di fusione BCR::ABL1, che trasforma le cellule staminali ematopoietiche in cellule leucemiche. Il monitoraggio del trascritto BCR::ABL1 è il metodo standard per valutare la risposta ai TKI (inibitori delle tirosin-chinasi). Tuttavia, recenti evidenze suggeriscono che marcatori infiammatori (come ROCK2 e IGFBP6), fattori epigenetici (come BMI1, EZH2) e i polimorfismi di PD-L1 potrebbero rappresentare nuovi biomarcatori per monitorare efficacia terapeutica e progressione della malattia. In questo studio, su 21 pazienti affetti da LMC, abbiamo valutato l'espressione genica e i polimorfismi di PD-L1 al momento della diagnosi e dopo 12 mesi di trattamento. È emersa una correlazione significativa tra bassa espressione di EZH2 e migliore sopravvivenza libera da eventi. A 12 mesi, l’espressione di ROCK2 e PD-L1 aumentava, mentre quella di EZH2 e BMI1 diminuiva nei pazienti con risposta molecolare profonda. I polimorfismi di PD-L1 non influenzavano significativamente l’espressione. I risultati suggeriscono un possibile asse regolatorio ROCK2–PD-L1, già descritto nei tumori solidi, anche nella LMC, aprendo a nuove strategie terapeutiche personalizzate.
Chronic myeloid leukemia (CML) is defined by the BCR::ABL1 fusion protein, which drives the transformation of hematopoietic stem cells into leukemic cells. Monitoring the BCR::ABL1 transcript is the gold standard for evaluating response to tyrosine kinase inhibitors (TKIs). However, recent findings indicate that inflammatory markers (such as ROCK2 and IGFBP6), epigenetic regulators (including BMI1, EZH2) and PD-L1 polymorphisms may serve as additional biomarkers to track disease progression and treatment efficacy. This study analyzed 21 CML patients at diagnosis and after 12 months of TKI therapy, measuring gene expression via ddPCR and PD-L1 polymorphisms via RT-PCR. Lower EZH2 expression at baseline was significantly associated with prolonged event-free survival. After 12 months, ROCK2 and PD-L1 levels increased, while EZH2 and BMI1 decreased in patients achieving deeper molecular responses. No significant association was found between PD-L1 variants and gene expression. The results suggest a regulatory ROCK2–PD-L1 axis similar to mechanisms observed in solid tumors, offering new therapeutic perspectives in CML.
Chronic myeloid leukemia (CML) is defined by the BCR::ABL1 fusion protein, which drives the transformation of hematopoietic stem cells into leukemic cells. Monitoring the BCR::ABL1 transcript is the gold standard for evaluating response to tyrosine kinase inhibitors (TKIs). However, recent findings indicate that inflammatory markers (such as ROCK2 and IGFBP6), epigenetic regulators (including BMI1, EZH2) and PD-L1 polymorphisms may serve as additional biomarkers to track disease progression and treatment efficacy. This study analyzed 21 CML patients at diagnosis and after 12 months of TKI therapy, measuring gene expression via ddPCR and PD-L1 polymorphisms via RT-PCR. Lower EZH2 expression at baseline was significantly associated with prolonged event-free survival. After 12 months, ROCK2 and PD-L1 levels increased, while EZH2 and BMI1 decreased in patients achieving deeper molecular responses. No significant association was found between PD-L1 variants and gene expression. The results suggest a regulatory ROCK2–PD-L1 axis similar to mechanisms observed in solid tumors, offering new therapeutic perspectives in CML.
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