Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia
© 2024. The Author(s)..
Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph+ B-ALL cells secrete the chemokine CXCL16, which in turn promotes Th17 differentiation, attracts Th17 cells and forms a positive feedback loop supporting leukemia progression. These data demonstrate an involvement of Th17 cells in Ph+ B-ALL progression and suggest potential therapeutic options for Ph+ B-ALL with Th17-enriched niches.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 03. Jan., Seite 203 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Feng [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
8A1O1M485B |
|---|
| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 06.01.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-023-44270-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366627473 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366627473 | ||
| 003 | DE-627 | ||
| 005 | 20240108142807.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240108s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-023-44270-3 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1251.xml |
| 035 | |a (DE-627)NLM366627473 | ||
| 035 | |a (NLM)38172124 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Feng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.01.2024 | ||
| 500 | |a Date Revised 06.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph+ B-ALL cells secrete the chemokine CXCL16, which in turn promotes Th17 differentiation, attracts Th17 cells and forms a positive feedback loop supporting leukemia progression. These data demonstrate an involvement of Th17 cells in Ph+ B-ALL progression and suggest potential therapeutic options for Ph+ B-ALL with Th17-enriched niches | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Imatinib Mesylate |2 NLM | |
| 650 | 7 | |a 8A1O1M485B |2 NLM | |
| 650 | 7 | |a Fusion Proteins, bcr-abl |2 NLM | |
| 650 | 7 | |a EC 2.7.10.2 |2 NLM | |
| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 700 | 1 | |a Li, Yunxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zhaona |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Wenbin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Luyao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Chenxi |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jinmei |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jiaojiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jichao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaowei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ping-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Mingzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Sizhou |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Billy Wai-Lung |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhuo-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Erlie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Bing |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 03. Jan., Seite 203 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:03 |g month:01 |g pages:203 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-023-44270-3 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 03 |c 01 |h 203 | ||