ROR1 is an accurate and reliable marker of minimal residual disease in chronic lymphocytic leukaemia

Propris, Maria Stefania De; Intoppa, Stefania; Milani, Maria Laura; Mariglia, Paola; Nardacci, Maria Grazia; Peragine, Nadia; Foà, Robin; Guarini, Anna

doi:10.1111/bjh.16910

Cited by 6 publications

(5 citation statements)

References 14 publications

(15 reference statements)

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“…In 2018, Rawstron et al published a consensus recommending a panel of markers, including ROR1 along with CD43, CD79b, CD81, CD200, and CD10, and showed the utility and importance of ROR1 in refining the diagnosis of borderline cases (Rawstron et al, 2018). De Propris and colleagues have demonstrated that the expression and MFI of ROR1 were preserved in CLL cells during and after different treatment (De Propris et al, 2020). These properties make ROR1 an attractive candidate for MRD monitoring in combination with other core molecules, as proposed by ERIC.…”

Section: Discussionmentioning

confidence: 99%

Performance of a novel eight‐color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia

Chen,

Zhao

et al. 2024

Cytometry Part B Clinical

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BackgroundMeasurable residual disease (MRD) is an important prognostic indicator of chronic lymphocytic leukemia (CLL). Different flow cytometric panels have been developed for the MRD assessment of CLL in Western countries; however, the application of these panels in China remains largely unexplored.MethodsOwing to the requirements for high accuracy, reproducibility, and comparability of MRD assessment in China, we investigated the performance of a flow cytometric approach (CD45‐ROR1 panel) to assess MRD in patients with CLL. The European Research Initiative on CLL (ERIC) eight‐color panel was used as the “gold standard.”ResultsThe sensitivity, specificity, and concordance rate of the CD45‐ROR1 panel in the MRD assessment of CLL were 100% (87/87), 88.5% (23/26), and 97.3% (110/113), respectively. Two of the three inconsistent samples were further verified using next‐generation sequencing. In addition, the MRD results obtained from the CD45‐ROR1 panel were positively associated with the ERIC eight‐color panel results for MRD assessment (R = 0.98, p < 0.0001). MRD detection at low levels (≤1.0%) demonstrated a smaller difference between the two methods (bias, −0.11; 95% CI, −0.90 to 0.68) than that at high levels (>1%). In the reproducibility assessment, the bias was smaller at three data points (within 24, 48, and 72 h) in the CD45‐ROR1 panel than in the ERIC eight‐color panel. Moreover, MRD levels detected using the CD45‐ROR1 panel for the same samples from different laboratories showed a strong statistical correlation (R = 0.99, p < 0.0001) with trivial interlaboratory variation (bias, 0.135; 95% CI, −0.439 to 0.709). In addition, the positivity rate of MRD in the bone marrow samples was higher than that in the peripheral blood samples.ConclusionsCollectively, this study demonstrated that the CD45‐ROR1 panel is a reliable method for MRD assessment of CLL with high sensitivity, reproducibility, and reliability.

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Section: Discussionmentioning

confidence: 99%

Performance of a novel eight‐color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia

Chen,

Zhao

et al. 2024

Cytometry Part B Clinical

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“…Although treatment could explain this difference, a study reported that the expression and the mean fluorescence intensity of ROR1 were maintained by CLL cells regardless the type of treatment received in GIMEMA trials: ibrutinib + rituximab (CLL1114), venetoclax + rituximab (CLL1518), fludarabine + cyclophosphamide + ofatumumab (CLL0911); ibrutinib + ofatumumab (CLL1215). Particularly, this expression was detected always on residual CLL cells 86 . Transgenic mice expressing both ROR1 and TCL1 developed lymphocytosis and splenomegaly resembling human CLL.…”

Section: Impact Of Ror1 In Signaling Diagnosis and Prognosis Of Cllmentioning

confidence: 92%

“…Particularly, this expression was detected always on residual CLL cells. 86 Transgenic mice expressing both ROR1 and TCL1 developed lymphocytosis and splenomegaly resembling human CLL. In such cells, ROR1 and TCL1, a coactivator of AKT, were found to complex, leading to AKT activation, increased proliferation and resistance to apoptosis.…”

Section: Daneshmanesh Et Al Demonstrated That Anti-ror1 Mouse Mabmentioning

confidence: 99%

“…33,84 Importantly, after all treatment combinations, ROR1 was consistently present on residual CLL cells, aiding in detecting measurable residual disease (MRD) as alongside markers such as CD5 and CD19. [85][86][87] ROR1 evaluation can substitute the evaluation of the light chain, a marker used to detect CLL cells, not MRD. Furthermore, using recursive partitioning, a study defined a threshold for distinguishing CLL cells with elevatedlevel versus low-level ROR1 surface expression.…”

Section: Daneshmanesh Et Al Demonstrated That Anti-ror1 Mouse Mabmentioning

confidence: 99%

“…Quantitative immune fluorescence studies reported surface ROR1 molecules range from 1000 to 11,000 per cell 33,84 . Importantly, after all treatment combinations, ROR1 was consistently present on residual CLL cells, aiding in detecting measurable residual disease (MRD) as alongside markers such as CD5 and CD19 85–87 . ROR1 evaluation can substitute the evaluation of the light chain, a marker used to detect CLL cells, not MRD.…”

Section: Impact Of Ror1 In Signaling Diagnosis and Prognosis Of Cllmentioning

confidence: 99%

See 2 more Smart Citations

How receptor tyrosine kinase‐like orphan receptor 1 meets its partners in chronic lymphocytic leukemia

Mouawad,

Ruggeri,

Capasso

et al. 2024

Hematological Oncology

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Chronic lymphocytic leukemia (CLL) is the most common leukemia in western societies, recognized by clinical and molecular heterogeneity. Despite the success of targeted therapies, acquired resistance remains a challenge for relapsed and refractory CLL, as a consequence of mutations in the target or the upregulation of other survival pathways leading to the progression of the disease. Research on proteins that can trigger such pathways may define novel therapies for a successful outcome in CLL such as the receptor tyrosine kinase‐like orphan receptor 1 (ROR1). ROR1 is a signaling receptor for Wnt5a, with an important role during embryogenesis. The aberrant expression on CLL cells and several types of tumors, is involved in cell proliferation, survival, migration as well as drug resistance. Antibody‐based immunotherapies and small‐molecule compounds emerged to target ROR1 in preclinical and clinical studies. Efforts have been made to identify new prognostic markers having predictive value to refine and increase the detection and management of CLL. ROR1 can be considered as an attractive target for CLL diagnosis, prognosis, and treatment. It can be clinically effective alone and/or in combination with current approved agents. In this review, we summarize the scientific achievements in targeting ROR1 for CLL diagnosis, prognosis, and treatment.

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The future of laboratory testing in chronic lymphocytic leukaemia

2021

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ROR1 is an accurate and reliable marker of minimal residual disease in chronic lymphocytic leukaemia

Abstract: Additional supporting information may be found online in the Supporting Information section at the end of the article. Data S1. Detailed description of the methods.

Cited by 6 publications

References 14 publications

Performance of a novel eight‐color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia

Performance of a novel eight‐color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia

How receptor tyrosine kinase‐like orphan receptor 1 meets its partners in chronic lymphocytic leukemia

The future of laboratory testing in chronic lymphocytic leukaemia

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