An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies <scp>CD</scp>13 as a useful marker for diagnostic subtyping

Lau, Hubert D.; Nagy, Alexandra; Atwater, Susan K.; Cascio, Michael J.; Ohgami, Robert S.

doi:10.1111/ijlh.12909

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…Although specificity for LPL/WM cells was higher in CD13 than VS38 (Table 7), CD13-positive B cells were only part of whole LPL/WM cells. In previous reports, CD13 stains LPL/WM cells with high specificity; however, positive rates were low (Lau et al, 2018;Raimbault et al, 2019), consistently with our data. We believe that VS38-gating can simultaneously allow capturing most LPL/WM cells while narrowing down a subset of LPL/WM cells from a heterogeneous background of mostly normal B cells (Table 7 and Figure 5).…”

Section: Evaluation Of Immunophenotype In Lpl/wm Cellssupporting

confidence: 92%

“…Lymphoma cells in the bone marrow are important to identify at the time of LPL/WM diagnosis, and the presence of an MYD88 L265P mutation is especially useful for determining this (Jiménez et al, 2013;Varettoni et al, 2013;Xu et al, 2013). Lymphoma cells express CD13, CD25, and CD27 in patients with LPL/WM (Lau et al, 2018;Paiva et al, 2014). However, varying positive rates and expression levels of Abbreviations: BCL, B cell lymphoma; CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; HCL-v, hairy cell leukemia-variant; LPL, lymphoplasmacytic lymphoma; MCL, mantle cell lymphoma; SMZL, splenic marginal zone lymphoma; WM, Waldenström macroglobulinemia.…”

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confidence: 99%

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VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia

Mizuta

Yamane

Mononobe

et al. 2021

Cytometry Part B Clinical

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Background: Multi-parametric flow cytometry (MFC) is a helpful tool for detecting neoplastic cells in malignant lymphoma; however, lymphoma cells can be difficult to detect when characteristic immunophenotypic abnormalities are not evident. We evaluated the stainability of VS38, which is used for multiple myeloma, in normal and abnormal B cells using MFC to develop a new strategy for detecting lymphoma cells. Methods:We compared the median fluorescence intensity of VS38 staining in lymphocytes from patients without hematopoietic neoplasms and in B cells from 26 patients with B cell lymphoma (BCL). To evaluate the performance of VS38 gating, we compared VS38-positive B cells with the percentages of BCL cells, and with the mutation ratios of MYD88 L265P measured by droplet digital PCR in patients with lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM).Results: CD27-positive memory B cells were stained with VS38, whereas normal lymphocytes were faintly stained. Lymphoma cells were stained with VS38 in 11 of 12 patients with LPL/WM, 3 of 3 with chronic lymphocytic leukemia, 3 of 5 with mantle cell lymphoma, 2 of 4 with follicular lymphoma, and 1 of 1 with splenic marginal zone lymphoma. The percentages of VS38-positive B cells in VS38-positive BCL were equivalent to those of lymphoma cells and the mutation ratios of MYD88 L265P in LPL/WM. Conclusions: VS38 identified neoplastic cells in plasma cell disorders and BCL. This might improve the accuracy of BCL diagnosis, especially in patients with LPL/WM.

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Section: Evaluation Of Immunophenotype In Lpl/wm Cellssupporting

confidence: 92%

mentioning

confidence: 99%

VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia

Mizuta

Yamane

Mononobe

et al. 2021

Cytometry Part B Clinical

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“…Aminopeptidases are involved in many human disorders, including autoimmune diseases and cancer. For example, aminopeptidase N (ANPEP alias CD13) is abnormally expressed in AML, B-cell acute lymphoblastic leukemia, and chronic lymphoblastic leukemia, where it may be used as a diagnostic or prognostic marker [6][7][8]. ANPEP is also expressed in a subset of Waldenström macroglobulinemia, MM, and plasma cell leukemias [9,10].…”

Section: Introductionmentioning

confidence: 99%

Aminopeptidase Expression in Multiple Myeloma Associates with Disease Progression and Sensitivity to Melflufen

Miettinen

Kumari

Traustadóttir

et al. 2021

Cancers

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Multiple myeloma (MM) is characterized by extensive immunoglobulin production leading to an excessive load on protein homeostasis in tumor cells. Aminopeptidases contribute to proteolysis by catalyzing the hydrolysis of amino acids from proteins or peptides and function downstream of the ubiquitin–proteasome pathway. Notably, aminopeptidases can be utilized in the delivery of antibody and peptide-conjugated drugs, such as melflufen, currently in clinical trials. We analyzed the expression of 39 aminopeptidase genes in MM samples from 122 patients treated at Finnish cancer centers and 892 patients from the CoMMpass database. Based on ranked abundance, LAP3, ERAP2, METAP2, TTP2, and DPP7 were highly expressed in MM. ERAP2, XPNPEP1, DPP3, RNPEP, and CTSV were differentially expressed between relapsed/refractory and newly diagnosed MM samples (p < 0.05). Sensitivity to melflufen was detected ex vivo in 11/15 MM patient samples, and high sensitivity was observed, especially in relapsed/refractory samples. Survival analysis revealed that high expression of XPNPEP1, RNPEP, DPP3, and BLMH (p < 0.05) was associated with shorter overall survival. Hydrolysis analysis demonstrated that melflufen is a substrate for aminopeptidases LAP3, LTA4H, RNPEP, and ANPEP. The sensitivity of MM cell lines to melflufen was reduced by aminopeptidase inhibitors. These results indicate critical roles of aminopeptidases in disease progression and the activity of melflufen in MM.

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“…Raponi et al reported CD22 expression among different subtypes of ALL as 83% of Pro-B, 96.4% of common B cell, 91.9% of Pre-B and 100% of the mature B cell ALL [70]. In mature B cell lymphoma, its expression has been reported as 95% in chronic lymphocytic leukemia, 89% in diffuse large B-cell lymphoma, 98% in follicular lymphoma, 96% in lymphoplasmacytic lymphoma and 100% in hairy cell, mantle cell, marginal zone, splenic marginal zone lymphomas and monoclonal B-lymphocytosis [71]. Hence CD22 can serve as a good target for therapy of B cell malignancies.…”

Section: Cd22 Positivity In Lymphoid Malignanciesmentioning

confidence: 99%

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Aujla

Liu

2019

Biomark Res

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B cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) frequently express CD19, CD20 and CD22 on the cell surfaces. Immunotherapeutic agents including antibodies and chimeric antigen receptor T cells are widely studied in clinical trials. Several antibody-drug conjugates (ADC) have been approved for clinical use (gemtuzumab ozogamicin in acute myeloid leukemia and brentuximab vedotin in Hodgkin lymphoma as well as CD30+ anaplastic large cell lymphoma). Inotuzumab ozogamicin (INO), a CD22 antibody conjugated with calicheamicin is one of the newest ADCs. INO has been approved for treatment of relapsed /refractory B cell precursor ALL. Multiple ongoing trials are evaluating its role in the relapsed /refractory B cell NHL. This review summarized recent development in INO applications for ALL and NHL.

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An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping

Abstract: CD13 expression is present more often in LPL- and FMC7-positive CLL/SLL than other mature B cell lymphoma subtypes and absent in cases of FL and may be a useful feature for diagnostic subtyping.

Cited by 6 publications

References 17 publications

VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia

VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia

Aminopeptidase Expression in Multiple Myeloma Associates with Disease Progression and Sensitivity to Melflufen

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

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