{"entity": "publication", "iuid": "cd7422c5b7fc40ee85e92641a7f51553", "timestamp": "2026-08-26T20:43:37.221Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cd7422c5b7fc40ee85e92641a7f51553.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cd7422c5b7fc40ee85e92641a7f51553"}}, "title": "Crosstalk between ROR1 and BCR pathways defines novel treatment strategies in mantle cell lymphoma.", "authors": [{"family": "Karvonen", "given": "Hanna", "initials": "H"}, {"family": "Chiron", "given": "David", "initials": "D"}, {"family": "Niininen", "given": "Wilhelmiina", "initials": "W"}, {"family": "Ek", "given": "Sara", "initials": "S"}, {"family": "Jerkeman", "given": "Mats", "initials": "M"}, {"family": "Moradi", "given": "Elaheh", "initials": "E"}, {"family": "Nykter", "given": "Matti", "initials": "M"}, {"family": "Heckman", "given": "Caroline A", "initials": "CA"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O"}, {"family": "Murum\u00e4gi", "given": "Astrid", "initials": "A"}, {"family": "Ungureanu", "given": "Daniela", "initials": "D"}], "type": "journal article", "published": "2017-11-14", "journal": {"title": "Blood Adv", "issn": "2473-9529", "volume": "1", "issue": "24", "pages": "2257-2268", "issn-l": null}, "abstract": "Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin B-cell lymphoma with poor prognosis due to drug resistance. Introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has markedly improved MCL therapy outcome, but drug resistance remains a challenge. The selective cell-surface expression of oncogenic receptor tyrosine kinase-like orphan receptor 1 (ROR1) pseudokinase in hematological malignancies has made this receptor a promising candidate for targeted therapy. We sought to identify the molecular mechanism underlying divergent ROR1-mediated apoptotic responses in MCL cell lines and primary samples. We show that targeting ROR1 expression resulted in downregulation of NF-\u03baB p65 levels and that activation of the NF-\u03baB pathway can antagonize ROR1-mediated apoptotic responses. High-throughput drug-sensitivity testing of MCL cells before and after ROR1 targeting revealed synergistic effects between cotargeting of ROR1 and the B-cell antigen receptor (BCR) or Bcl-2 family, underlining the high potential for ROR1-targeted therapies in overcoming MCL drug resistance. However, inhibition of the BCR pathway by targeted drugs such as ibrutinib can impair ROR1 expression and consequently ROR1-targeted treatments, underscoring the importance of inhibiting both pathways to augment cancer cell killing. Considering the central role of NF-\u03baB pathway activation in B-cell malignancies, this study highlights key factors that can modulate ROR1-targeted treatments in hematological cancers.", "doi": "10.1182/bloodadvances.2017010215", "pmid": "29296874", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5737127"}, {"db": "pii", "key": "2017/010215"}], "notes": [], "created": "2026-08-20T12:18:41.731Z", "modified": "2026-08-20T12:18:41.776Z"}