Academic Journal
TAK1 and TBK1 are Differentially Required by GMP- and LMPP-like Leukemia Stem Cells
| العنوان: | TAK1 and TBK1 are Differentially Required by GMP- and LMPP-like Leukemia Stem Cells |
|---|---|
| المؤلفون: | Runde, Austin P, Cannova, Joseph Michael, Mack, Ryan, Joshi, Kanak, Sellin, Mark, Youmaran, Allan, Lenz, Mattias, Thalla, Rohit, Wei, Wei, Breslin, Peter, S.J., Zhang, Jiwang |
| المصدر: | School of Medicine |
| بيانات النشر: | Loyola eCommons |
| سنة النشر: | 2023 |
| المجموعة: | Loyola University Chicago: Loyola eCommons |
| مصطلحات موضوعية: | acute myeloid leukemia, chemotherapy, chloroma, CSF1R, FLT3, hematology, MLL-AF9, oncology, stem cells, TAK1, TBK1, TLR, Cancer Biology, Cell Biology, Chemical and Pharmacologic Phenomena, Laboratory and Basic Science Research |
| الوصف: | Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA+), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients experience relapse within 3 years from their diagnosis. Additionally, 30-40% of patients present with refractory AML, experiencing little to no benefit from frontline treatment. AML relapses when a pool of undetectable, CTx-resistant leukemia stem cells (LSCs) survives & proliferates after frontline CTx [1]. Notably, the poor performance status of many AML patients precludes use of the standard CTx regimen; while reduced-intensity CTx still offers therapeutic benefit, it is less effective at killing LSCs and, as a result, relapse is more likely. Goardon, et al. determined that AML patients harbor two types of LSCs: granulocyte-macrophage progenitor (GMP)-like LSCs and FLT3+ lymphoid-primed multipotential progenitor (LMPP)-like LSCs [2]. Eradication of both types of LSCs is necessary to maintain CR in AML. Our group and others have established that ~40% of AML patients express upregulated Toll-like receptor (TLR) signaling (TLR+). TLR+ disease is associated with specific genetic abnormalities, such as MLL rearrangements (MLL-r+), and is inversely associated with prognosis (Figure 1) [3,4]. TLR+ AML represents a challenging, treatment-sparse subset of an already difficult-to-treat disease. To study TLR+ AML, we utilize an MLL-r+ model using the MLL-AF9 oncogene. We have also demonstrated that both GMP- and LMPP-like LSCs require TLR-associated Ser/Thr protein kinases for their survival [5-7]. ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| Relation: | https://ecommons.luc.edu/medicine/6; https://ecommons.luc.edu/context/medicine/article/1005/viewcontent/TBK1_POSTER_apr_SAD_2023.pdf |
| الاتاحة: | https://ecommons.luc.edu/medicine/6 https://ecommons.luc.edu/context/medicine/article/1005/viewcontent/TBK1_POSTER_apr_SAD_2023.pdf |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/3.0/ |
| رقم الانضمام: | edsbas.44A9ED04 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |