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Article
Open AccessCorrection: a phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic HER2-negative breast cancer
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Open AccessA phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic HER2-negative breast cancer
Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that z...
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Article
Open AccessAssociation of baseline ROR1 and ROR2 gene expression with clinical outcomes in the I-SPY2 neoadjuvant breast cancer trial
ROR1 and ROR2 are Type 1 tyrosine kinase-like orphan receptors for Wnt5a that are associated with breast cancer progression. Experimental agents targeting ROR1 and ROR2 are in clinical trials. This study evalu...
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Article
Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome
Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we c...
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Article
Molecular map of chronic lymphocytic leukemia and its impact on outcome
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymp...
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Article
Open AccessHigh expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia
Although the BH3-mimetic venetoclax is highly cytotoxic for chronic lymphocytic leukemia (CLL) cells, some patients with CLL fail to clear minimal residual disease (MRD). We examined the CLL cells of seven suc...
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Article
Open AccesscyCombine allows for robust integration of single-cell cytometry datasets within and across technologies
Combining single-cell cytometry datasets increases the analytical flexibility and the statistical power of data analyses. However, in many cases the full potential of co-analyses is not reached due to technica...
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Article
Open AccessPolygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans
Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-suscepti...
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Article
Multifunctional barcoding with ClonMapper enables high-resolution study of clonal dynamics during tumor evolution and treatment
Lineage-tracing methods have enabled characterization of clonal dynamics in complex populations, but generally lack the ability to integrate genomic, epigenomic and transcriptomic measurements with live-cell m...
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Article
Open AccessWnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism
Patients with chronic lymphocytic leukemia (CLL) have high plasma-levels of Wnt5a, which can induce phosphorylation of ERK1/2 and enhance CLL-cell proliferation. Such effects could be inhibited by treatment wi...
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Article
Open AccessRecurrent XPO1 mutations alter pathogenesis of chronic lymphocytic leukemia
Exportin 1 (XPO1/CRM1) is a key mediator of nuclear export with relevance to multiple cancers, including chronic lymphocytic leukemia (CLL). Whole exome sequencing has identified hot-spot somatic XPO1 point mutat...
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Article
NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia
Progression of chronic lymphocytic leukemia (CLL) and resistance to therapy are affected by tumor microenvironmental factors. One such factor is B-cell activating factor (BAFF), a cytokine that is produced mai...
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Article
Open AccessLong-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study
RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged ≥65 years (n = 269) were randomized 1:1 to once-dail...
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Article
Aurora B induces epithelial–mesenchymal transition by stabilizing Snail1 to promote basal-like breast cancer metastasis
Aurora B is a serine/threonine kinase that has been implicated in regulating cell proliferation in distinct cancers, including breast cancer. Here we show that Aurora B expression is elevated in basal-like bre...
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Article
Open AccessGenetic dynamics in untreated CLL patients with either stable or progressive disease: a longitudinal study
Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We...
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Open AccessWnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis
ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a als...
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Article
Plasma B-Cell Maturation Antigen Levels are Elevated and Correlate with Disease Activity in Patients with Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a malignancy of late B cells. In another late B-cell malignancy (multiple myeloma), levels of solubilized B-cell maturation antigen (sBCMA) are elevated and predict outcomes.
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Article
Growth dynamics in naturally progressing chronic lymphocytic leukaemia
How the genomic features of a patient’s cancer relate to individual disease kinetics remains poorly understood. Here we used the indolent growth dynamics of chronic lymphocytic leukaemia (CLL) to analyse the g...
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Article
Open AccessWnt5a causes ROR1 to complex and activate cortactin to enhance migration of chronic lymphocytic leukemia cells
Chronic lymphocytic leukemia cells (CLL) migrate between the blood and lymphoid tissues in response to chemokines. Such migration requires structured cytoskeletal-actin polymerization, which may involve the pr...
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Chimeric Antigen Receptor T Cells: Antigen Selection, CAR Development, and Data in Neoplastic Hematology
Adoptive cellular therapy for cancer and other diseases is rapidly becoming one of the most actively studied areas. Genetically modified chimeric antigen receptor T cells provide exciting potential for curativ...
