A Novel Diagnostic B-Cell Marker to Distinguish Neoplastic B Lymphoblasts From Hematogones

Silvia Saumell Tutusaus, MD, PhD; Elaina Pirruccello, DO; Franklin Fuda, DO; Hywyn Churchill, MD, PhD; Dong Chen, MD, PhD; Cheng Cheng Zhang, PhD; Weina Chen, MD, PhD

Disclosures

Am J Clin Pathol. 2021;156(6):941-949. 

In This Article

Abstract and Introduction

Abstract

Objectives: New B-cell markers are needed for monitoring B lymphoblastic leukemia (B-ALL) in the era of immunotherapies directed against CD19 and CD22. The expression of leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) on hematogones in bone marrow (BM) and neoplastic B lymphoblasts has not yet been systematically investigated.

Methods: We assessed LILRB1 expression pattern on B cells in 19 control BMs and 22 B-ALL cases by flow cytometry.

Results: In all cases, mature B cells and hematogones exhibited a consistent pattern of LILRB1 expression with variable intensity over different stages of maturation, including a characteristic V-shaped pattern on hematogones. While neoplastic B lymphoblasts in all cases expressed LILRB1, the pattern of expression was distinctly abnormal relative to hematogones (loss of the dynamic pattern in all cases and abnormal expression levels in 83% of cases).

Conclusions: LILRB1 is a novel diagnostic B-cell marker to aid in distinguishing neoplastic B lymphoblasts from hematogones.

Introduction

Multiparameter flow cytometry (MFC) immunophenotyping is instrumental in diagnosing B-lymphoblastic leukemia (B-ALL) and in detecting residual disease in conjunction with morphologic and genetic studies.[1–4] The principle applied in MFC is to identify neoplastic immature B cells (B lymphoblasts) that are immunophenotypically aberrant relative to their normal counterparts, maturing B-cell precursors (hematogones), by using appropriately selected antibody panels.[2,4–6] The backbone of B-cell markers used in both Children's Oncology Group and EuroFlow panels is CD19. CD20, frequently absent in B-ALL, is also present in both panels.

Recently developed immunotherapies (eg, chimeric antigen receptor directed against CD19 expressed on neoplastic B lymphoblasts) and anti-CD22 immunotoxin have emerged as promising targeted therapies in treating relapsed and refractory B-ALL.[7] Such antigen-based therapy may compromise the ability to use CD19 and CD22 for identifying neoplastic B lymphoblasts since their expressions may be diminished to absent posttherapeutically and patients may relapse with either CD19-negative and/or CD19-positive B-ALL.[7,8] A new gating strategy using other B-cell markers, such as CD24, is a topic of active investigation,[9,10] as there is a need to explore novel diagnostic B-cell markers for identifying neoplastic B lymphoblasts to improve residual disease detection. One such novel marker is LILRB1.

LILRB1 (CD85j, ILT2, or LIR-1) belongs to the type I transmembrane inhibitory leukocyte immunoglobulin-like receptor subfamily B member (LILRB) that can inhibit immune cell activation.[11,12] Although LILRB1 is known to be expressed on lymphocytes, including B cells, and on monocytes,[12,13] its expression pattern on hematogones, mature B cells, and neoplastic B lymphoblasts has not yet been systematically investigated in the clinical setting. The goal of our study is twofold: to evaluate the expression pattern of LILRB1 on hematogones and mature B cells and to assess whether the differential expression pattern of LILRB1 on neoplastic B lymphoblasts permits distinction from hematogones.

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