DIEAML · Deciphering immune evasion of Acute Myeloid Leukemia
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2022-09-01 → 2024-12-01
- Финансиране от ЕС
- 162 806 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Острата миелоидна лейкемия се изследва чрез анализ на стволовите ракови клетки, които могат да рестартират болестта след лечение. Разбирането на тези клетки помага за разработването на стратегии, които да намалят рискът от рецидив и да подобрят шансовете за дълготрайна ремисия.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Deciphering immune evasion of Acute Myeloid Leukemia
Cancer is the leading cause of death in people over the age of 50. It can develop in any tissue or organ of the body and, at its core, is caused by the uncontrolled growth of abnormal cells. One particularly aggressive form of cancer is Acute Myeloid Leukemia (AML), the most common type of leukemia in adults. AML is difficult to treat, with a high risk of relapse and death. One of the biggest challenges in AML treatment is therapy resistance—when cancer cells survive treatment and cause the disease to return. A key reason for this is the presence of leukemia stem cells (LSCs), a rare subset of cancer cells that have the ability to restart the disease, much like normal stem cells regenerate healthy tissue. Even after treatment, these LSCs can remain hidden in the body, leading to relapse. To improve survival rates and long-term outcomes for AML patients, researchers urgently need to develop new treatment strategies that specifically target and eliminate LSCs. Finding ways to overcome therapy resistance could significantly reduce relapses and offer patients a better chance at lasting remission.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Acute Myeloid Leukemia (AML) is the most common adult leukemia, with a high frequency of relapse and mortality. After therapy, the persistence of rare leukemia stem cells (LSCs) with disease initiating and therefore stem cell-like properties is a likely cause for relapse. Therefore, novel therapeutic strategies to specifically eradicate LSCs are urgently needed. Natural Killer-cells (NK-cells) are innate immune cells capable of detecting cell surface ligands to trigger a cytotoxic response against diverse tumor cell types. NK-cells are activated either by missing inhibitory or activating ligands, such as known natural killer group 2D receptor ligands (NKG2DL), which become expressed on target cells upon cellular stress or malignant transformation. The groups of Drs. Trumpp, Lengerke and Salih recently described that LSCs evade the recognition from NK-Cells by repressing NKG2DL expression. Importantly, inhibition of Poly [ADP-ribose] polymerase 1 (PARP1) in a subclass of CD34+ AML patient samples reactivated NKG2DL expression and, when combined with allogeneic NK-Cell therapy, eradicated AML in xenotransplantation models. The goal of this proposal is to systematically discover novel NKG2DL regulators in AML to improve immunotherapeutic therapy options for a broad group of AML patients. I have identified monocytic differentiation and DNA hypermethylation as potentially opposing mechanisms of NKG2DL expression. I will combine single-cell transcriptomic and epigenomic interrogation of AML patient samples to discover how NKG2DL are activated during malignant differentiation and how these processes are impeded by DNA hypermethylation. These approaches, together with genome-wide CRISPR-dCas9 gain of function screens, will help identify master regulators of NKG2DL expression. Lastly, validation of these regulators in AML patient samples will expose vulnerabilities of AML for NK-cell based therapies and elaborate on the previously identified link with AML stemness.
Оригинален текст от CORDIS (на английски).
Участници
- DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG · HeidelbergКоординаторГермания
Връзки
Данни: CORDIS, © Европейски съюз