CD304/neuropilin‐1 is a very useful and dependable marker for the measurable residual disease assessment of B‐cell precursor acute lymphoblastic leukemia

Abstract

BackgroundMeasurable residual disease (MRD) assessment using multicolor flow cytometry (MFC) has become the center point of pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) risk stratification and therapeutic management. The addition of new markers can improve the accuracy and applicability of MFC‐based MRD assay further. Herein, we evaluated the utility of a new marker, CD304/neuropilin‐1, in the assessment of MFC‐based MRD.MethodsExpression patterns of CD304 were studied in leukemic blasts from BCP‐ALL patients and in normal precursor B cells (NPBC) from uninvolved non‐BCP‐ALL bone marrow samples using 10‐color MFC. MRD was monitored at end‐of‐induction (EOI; Days 35–40) and end‐of‐consolidation (Day 78–80) time points.ResultsWe studied CD304 expression in 300 pediatric BCP‐ALL patients and found it positive in BCP‐ALL blasts in 41.7% of diagnostic samples. It was significantly associated with ETV6‐RUNX1 (p < .001) as well as BCR‐ABL1 (p = .019) and inversely associated with TCF3‐PBX1 fusion gene (p = .0012). It was found clearly negative in NPBC. EOI‐MRD was detectable in 152/300 (50.7%; ≥0.01% in 35.33% and <0.01% in 15.33%) samples, in which CD304 was positive in 72/152 (47.4%) diagnostic and 63/152 (41.4%) MRD samples. It was positive in 45.7% (21/46) of low‐level (<0.01%) MRD samples. In comparison with diagnostic samples, its expression was retained in 68.06% (49/72), lost in 31.94% (23/72), and gained in 14/80 (17.5%) of EOI‐MRD samples.ConclusionsCD304 is commonly expressed in leukemic blasts of BCP‐ALL. It is very useful in distinguishing residual disease from hematogones and is a fairly dependable marker. Hence, it is a valuable addition for enhancing the sensitivity and applicability of MFC‐based MRD assay in BCP‐ALL.

Issue Highlights—July 2021

“…Among the authors' findings were a higher proportion of hyperdiploidy and a lower proportion of ETV6‐RUNX1 among MPO‐positive cases compared with MPO‐negative cases (McGinnis et al, 2021). These findings complement other recently described immunophenotypic‐genotypic correlations in B‐lymphoblastic leukemia (Collins et al, 2021; Gudapati et al, 2020).…”

Expression of CD304/neuropilin‐1 in adult b‐cell lymphoblastic leukemia/lymphoma and its utility for the measurable residual disease assessment

“…Briefly, the "first pull" of 0.5‐0.7 mL of BM aspirate sample was processed using Euroflow bulk lysis protocol 9 . A 10‐color MFC panel, described previously, 34 was used for MRD evaluation (Table ). Approximately 4‐5 million events were analyzed at the end of induction (EOI; Days 35‐40), end of consolidation (EOC; Days 78‐80), and subsequent follow‐up time points (SFU) from BM samples.…”

Blast size‐specific flowcytometric ploidy assessment using FxCycleTM Violet dye and its correlation with conventional cytogenetic ploidy in pediatric precursor B‐lineage acute lymphoblastic leukemia patients

“…Prognostic work up by FCM‐ploidy, conventional banding karyotyping, and i‐FISH panel to identify BCR‐ABL1 fusion, ETV‐RUNX1 fusion, i AMP21 , TCF3‐PBX1 fusion, and KMT2A rearrangement were routinely performed for all pediatric B‐ALL patients diagnosed at our institute. After informed consent from parents or legal guardians, the children were treated with risk‐adapted Indian childhood collaborative leukemia group (ICiCLe) protocol 15 …”