Nejvíce citovaný článek - PubMed ID 27185377
COBLL1, LPL and ZAP70 expression defines prognostic subgroups of chronic lymphocytic leukemia patients with high accuracy and correlates with IGHV mutational status
Chronic lymphocytic leukemia is a disease with up-regulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low. Importantly, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 have an unfavorable disease course with short overall survival and time to second treatment. COBLL1 serves as an independent molecular marker for overall survival in chronic lymphocytic leukemia patients with unmutated IGHV. In addition, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 show impaired motility and chemotaxis towards CCL19 and CXCL12 as well as enhanced B-cell receptor signaling pathway activation demonstrated by increased PLCγ2 and SYK phosphorylation after IgM stimulation. COBLL1 expression also changes during B-cell maturation in non-malignant secondary lymphoid tissue with a higher expression in germinal center B cells than naïve and memory B cells. Our data thus suggest COBLL1 involvement not only in chronic lymphocytic leukemia but also in B-cell development. In summary, we show that expression of COBLL1, encoding novel ROR1-binding partner, defines chronic lymphocytic leukemia subgroups with a distinct response to microenvironmental stimuli, and independently predicts survival of chronic lymphocytic leukemia with unmutated IGHV.
- MeSH
- analýza přežití MeSH
- chronická lymfatická leukemie klasifikace diagnóza genetika mortalita MeSH
- lidé MeSH
- mutace MeSH
- pohyb buněk MeSH
- polarita buněk MeSH
- prognóza MeSH
- signální dráha Wnt MeSH
- sirotčí receptory podobné receptoru tyrosinkinasy metabolismus MeSH
- těžké řetězce imunoglobulinů genetika MeSH
- transkripční faktory metabolismus MeSH
- variabilní oblast imunoglobulinu genetika MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- COBLL1 protein, human MeSH Prohlížeč
- ROR1 protein, human MeSH Prohlížeč
- sirotčí receptory podobné receptoru tyrosinkinasy MeSH
- těžké řetězce imunoglobulinů MeSH
- transkripční faktory MeSH
- variabilní oblast imunoglobulinu MeSH
