cad a22 4500 555259358 20190330042911.0 cr unu---uuuuu 190205e20190301xx s 000 0 eng 10.1038/s41388-018-0594-4 doi (ZORA)oai:www.zora.uzh.ch:161590 610 ddc 30532071 pmid Bone marrow T helper cells with a Th1 phenotype induce activation and proliferation of leukemic cells in precursor B acute lymphoblastic leukemia patients [Elektronische Daten] [Sabrina Traxel, Linda Schadt, Tatjana Eyer, Vanessa Mordasini, Claudine Gysin, Ludvig A Munthe, Felix Niggli, David Nadal, Simone Bürgler] closedAccess eu-repo Precursor B cell acute lymphoblastic leukemia (BCP-ALL) constitutes the leading cause of cancer-related death in children. While chromosomal alterations contribute to BCP-ALL pathogenesis, they are insufficient for leukemia development. Epidemiological data and evidence from a mouse model suggest that immune responses to infections may trigger the emergence of leukemia, but the mechanisms remain unclear. Here, we show that T helper (Th) cells from bone marrow of pediatric BCP-ALL patients can be attracted and activated by autologous BCP-ALL cells. Bone-marrow Th cells supportively interacted with BCP-ALL cells, inducing upregulation of important surface molecules and BCP-ALL cell proliferation. These Th cells displayed a Th1-like phenotype and produced high levels of IFN-γ. IFN-γ was responsible for the upregulation of CD38 in BCP-ALL cells, a molecule which we found to be associated with early relapse, and accountable for the production of IP-10, a chemokine involved in BCP-ALL migration and drug resistance. Thus, our data provide mechanistic support for an involvement of Th cell immune responses in the propagation of BCP-ALL and suggest that BCP-ALL cell-supportive Th cells may serve as therapeutic target. Medical Clinic zora Genetics, Cancer Research, Molecular Biology zora Traxel Sabrina joint author Schadt Linda joint author Eyer Tatjana joint author Mordasini Vanessa joint author Gysin Claudine joint author Munthe Ludvig A. joint author Niggli Felix joint author Nadal David joint author Bürgler Simone joint author Oncogene 38(13):2420-2431 https://www.zora.uzh.ch/161590 text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/161590 text/html WWW-Backlink auf das Repository ZORA 700 1- Traxel Sabrina joint author ZORA 700 1- Schadt Linda joint author ZORA 700 1- Eyer Tatjana joint author ZORA 700 1- Mordasini Vanessa joint author ZORA 700 1- Gysin Claudine joint author ZORA 700 1- Munthe Ludvig A. joint author ZORA 700 1- Niggli Felix joint author ZORA 700 1- Nadal David joint author ZORA 700 1- Bürgler Simone joint author ZORA 773 0- Oncogene 38(13):2420-2431 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article closedAccess