Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay

Undetectable minimal residual disease (MRD) in Chronic Lymphocytic Leukemia (CLL) has a favorable prognostic outcome compared with MRD that can be detected. This study investigated a flow cytometric assay (CD160-ROR1FCA) targeting the tumor-specific antigens CD160 and receptor tyrosine kinase-like o...

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Main Authors: Timothy W. Farren, Kaushik S. Sadanand, Samir G. Agrawal
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2020.597730/full
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author Timothy W. Farren
Timothy W. Farren
Kaushik S. Sadanand
Samir G. Agrawal
Samir G. Agrawal
author_facet Timothy W. Farren
Timothy W. Farren
Kaushik S. Sadanand
Samir G. Agrawal
Samir G. Agrawal
author_sort Timothy W. Farren
collection DOAJ
description Undetectable minimal residual disease (MRD) in Chronic Lymphocytic Leukemia (CLL) has a favorable prognostic outcome compared with MRD that can be detected. This study investigated a flow cytometric assay (CD160-ROR1FCA) targeting the tumor-specific antigens CD160 and receptor tyrosine kinase-like orphan receptor 1 (ROR1), along with CD2, CD5, CD19, CD45. CD160-ROR1FCA was compared with the originally published 8-colour European Research Initiative for CLL (ERIC) gold-standard assay for CLL MRD detection. CD160-ROR1FCA had a limit of detection of 0.001% and showed strong correlation with ERIC (R = 0.98, p < 0.01) with negligible differences in MRD detection (bias -0.3152 95%CI 5.586 to -6.216). Using CD160-ROR1FCA, increased expression of both CD160 and ROR1 was found in Monoclonal B cell Lymphocytosis (MBL) compared to low-level polyclonal B-cell expansions (p < 0.01). Patients in CR and with undetectable MRD had a longer EFS (not reached) than those in CR but with detectable MRD (756 days, p < 0.01) versus 113 days in patients with partial remission (p < 0.01). Patients with MRD levels of >0.01 to 0.1% had a longer EFS (2,333 days), versus levels between 0.1 to 1% (1,049 days). CD160-ROR1FCA is a novel assay for routine CLL MRD measurement and for MBL detection. MRD status assessed by CD160-ROR1FCA after CLL treatment correlated with EFS.
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spelling doaj.art-dc1827ef33404c9caf9d62ecb95e7c022022-12-21T18:14:29ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.597730597730Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 AssayTimothy W. Farren0Timothy W. Farren1Kaushik S. Sadanand2Samir G. Agrawal3Samir G. Agrawal4Department of Haemato-Oncology and Immunophenotyping (SIHMDS), Barts Health NHS Trust, London, United KingdomImmunobiology, Blizard Institute, Queen Mary University of London, London, United KingdomImmunobiology, Blizard Institute, Queen Mary University of London, London, United KingdomDepartment of Haemato-Oncology and Immunophenotyping (SIHMDS), Barts Health NHS Trust, London, United KingdomImmunobiology, Blizard Institute, Queen Mary University of London, London, United KingdomUndetectable minimal residual disease (MRD) in Chronic Lymphocytic Leukemia (CLL) has a favorable prognostic outcome compared with MRD that can be detected. This study investigated a flow cytometric assay (CD160-ROR1FCA) targeting the tumor-specific antigens CD160 and receptor tyrosine kinase-like orphan receptor 1 (ROR1), along with CD2, CD5, CD19, CD45. CD160-ROR1FCA was compared with the originally published 8-colour European Research Initiative for CLL (ERIC) gold-standard assay for CLL MRD detection. CD160-ROR1FCA had a limit of detection of 0.001% and showed strong correlation with ERIC (R = 0.98, p < 0.01) with negligible differences in MRD detection (bias -0.3152 95%CI 5.586 to -6.216). Using CD160-ROR1FCA, increased expression of both CD160 and ROR1 was found in Monoclonal B cell Lymphocytosis (MBL) compared to low-level polyclonal B-cell expansions (p < 0.01). Patients in CR and with undetectable MRD had a longer EFS (not reached) than those in CR but with detectable MRD (756 days, p < 0.01) versus 113 days in patients with partial remission (p < 0.01). Patients with MRD levels of >0.01 to 0.1% had a longer EFS (2,333 days), versus levels between 0.1 to 1% (1,049 days). CD160-ROR1FCA is a novel assay for routine CLL MRD measurement and for MBL detection. MRD status assessed by CD160-ROR1FCA after CLL treatment correlated with EFS.https://www.frontiersin.org/articles/10.3389/fonc.2020.597730/fullCD160ROR-1minimal/measurable residual diseasechronic lymphocytic leukemiamonoclonal B-cell lymphocytosisflow cytometry
spellingShingle Timothy W. Farren
Timothy W. Farren
Kaushik S. Sadanand
Samir G. Agrawal
Samir G. Agrawal
Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
Frontiers in Oncology
CD160
ROR-1
minimal/measurable residual disease
chronic lymphocytic leukemia
monoclonal B-cell lymphocytosis
flow cytometry
title Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
title_full Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
title_fullStr Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
title_full_unstemmed Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
title_short Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay
title_sort highly sensitive and accurate assessment of minimal residual disease in chronic lymphocytic leukemia using the novel cd160 ror1 assay
topic CD160
ROR-1
minimal/measurable residual disease
chronic lymphocytic leukemia
monoclonal B-cell lymphocytosis
flow cytometry
url https://www.frontiersin.org/articles/10.3389/fonc.2020.597730/full
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