CELLULAR AND MOLECULAR MECHANISMS OF CHEMORESISTANCE IN ACUTE MYELOID LEUKEMIA
type: CreativeWork
description: Acute Myeloid Leukemia (AML) remains an incurable disease, with a 5-year survival rate below 30%. While the introduction of new therapeutic approaches, such as targeted therapies and immunotherapy, has had a modest impact on AML prognosis, the standard treatment of AML is still based on chemotherapy regimens (like "7+3") that have been in use for over 50 years. Approximately 20% of patients do not respond to standard chemotherapy, and even among those who initially respond, around 50% eventually relapse due to the development of chemotherapy resistance. Chemoresistance is the cause of death for over 90% of AML patients. The mechanisms underlying chemoresistance in AML are not yet fully understood, and targeted therapies aimed at preventing chemoresistance are not currently available. Chemoresistance in AML is primarily driven by non-genetic mechanisms. While leukemic stem cells (LSCs) have been implicated, recent studies suggest that AML blasts that survive chemotherapy, known as Chemotherapy Persistent Blasts, enter a senescence-like and diapause state. Though they can contribute to disease recurrence, these Persistent Blasts are not inherently therapy-resistant as they revert to a drug-sensitive state upon drug withdrawal. However, a lack of robust in vivo models of clinical chemoresistance in human AML hinders our understanding of these mechanisms. To address this, I aimed to generate in vivo models of truly chemoresistant AML to investigate non-genetic mechanisms of chemotherapy resistance. I utilized mouse models of human AML, specifically Patient-Derived Xenografts (PDXs), to establish treatment protocols mimicking the standard "7+3" chemotherapy regimen used clinically. One model (AML9) mirrored the behavior of most patients treated with standard chemotherapy, exhibiting clinical remission followed by relapse. In contrast, the other model (AML20) showed a modest response to chemotherapy with rapid leukemia re-expansion. Notably, relapsed leukemias in both mod…
abstract: Acute Myeloid Leukemia (AML) remains an incurable disease, with a 5-year survival rate below 30%. While the introduction of new therapeutic approaches, such as targeted therapies and immunotherapy, has had a modest impact on AML prognosis, the standard treatment of AML is still based on chemotherapy regimens (like "7+3") that have been in use for over 50 years. Approximately 20% of patients do not respond to standard chemotherapy, and even among those who initially respond, around 50% eventually relapse due to the development of chemotherapy resistance. Chemoresistance is the cause of death for over 90% of AML patients. The mechanisms underlying chemoresistance in AML are not yet fully understood, and targeted therapies aimed at preventing chemoresistance are not currently available. Chemoresistance in AML is primarily driven by non-genetic mechanisms. While leukemic stem cells (LSCs) have been implicated, recent studies suggest that AML blasts that survive chemotherapy, known as Chemotherapy Persistent Blasts, enter a senescence-like and diapause state. Though they can contribute to disease recurrence, these Persistent Blasts are not inherently therapy-resistant as they revert to a drug-sensitive state upon drug withdrawal. However, a lack of robust in vivo models of clinical chemoresistance in human AML hinders our understanding of these mechanisms. To address this, I aimed to generate in vivo models of truly chemoresistant AML to investigate non-genetic mechanisms of chemotherapy resistance. I utilized mouse models of human AML, specifically Patient-Derived Xenografts (PDXs), to establish treatment protocols mimicking the standard "7+3" chemotherapy regimen used clinically. One model (AML9) mirrored the behavior of most patients treated with standard chemotherapy, exhibiting clinical remission followed by relapse. In contrast, the other model (AML20) showed a modest response to chemotherapy with rapid leukemia re-expansion. Notably, relapsed leukemias in both mod…
author: FRASCOLLA, SIMONE
language: eng
keywords: Acute Myeloid Leukemia, Chemoresistance, PDX model, IFN signalling, Settore MED/04 - Patologia Generale, Settore MEDS-02/A - Patologia generale
date published: 2025-01-21
date modified: 2026-07-27T20:18:51Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1125409