Details

Autor(en) / Beteiligte

• Abdelrasoul, Hend
• Vadakumchery, Anila
• Werner, Markus
• Lenk, Lennart
• Khadour, Ahmad
• Young, Marc
• El Ayoubi, Omar
• Vogiatzi, Fotini
• Krämer, Markus
• Schmid, Vera
• Chen, Zhengshan
• Yousafzai, Yasar
• Cario, Gunnar
• Schrappe, Martin
• Müschen, Markus
• Halsey, Christina
• Mulaw, Medhanie A
• Schewe, Denis M
• Hobeika, Elias
• Alsadeq, Ameera
• Jumaa, Hassan

Titel

Synergism between IL7R and CXCR4 drives BCR-ABL induced transformation in Philadelphia chromosome-positive acute lymphoblastic leukemia

Ist Teil von

• Nature communications, 2020-06, Vol.11 (1), p.3194-12, Article 3194

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Ph acute lymphoblastic leukemia (ALL) is characterized by the expression of an oncogenic fusion kinase termed BCR-ABL1. Here, we show that interleukin 7 receptor (IL7R) interacts with the chemokine receptor CXCR4 to recruit BCR-ABL1 and JAK kinases in close proximity. Treatment with BCR-ABL1 kinase inhibitors results in elevated expression of IL7R which enables the survival of transformed cells when IL7 was added together with the kinase inhibitors. Importantly, treatment with anti-IL7R antibodies prevents leukemia development in xenotransplantation models using patient-derived Ph  ALL cells. Our results suggest that the association between IL7R and CXCR4 serves as molecular platform for BCR-ABL1-induced transformation and development of Ph  ALL. Targeting this platform with anti-IL7R antibody eliminates Ph  ALL cells including those with resistance to commonly used ABL1 kinase inhibitors. Thus, anti-IL7R antibodies may provide alternative treatment options for ALL in general and may suppress incurable drug-resistant leukemia forms.