CD1c(+) myeloid dendritic cells in myeloid neoplasia.

We determined the normal level and phenotype of CD1c(+) myeloid dendritic cells (MDCs) in blood and bone marrow and evaluated the level of CD1c(+) MDCs in 295 myeloid neoplasms. CD1c(+) MDCs were increased above the mean level of non-neoplastic hospital controls in 18.0% (53/295) of myeloid malignancies, increased three standard deviations above the control mean in 14.2% (42/295) with a 10-fold or more increase compared to mean in 6.8% (20/295). Increased CD1c(+) MDCs were associated with chronic myelomonocytic leukemia (CMML) (12/24, 50%) and acute myeloid leukemia (AML) (31/140, 22%) with a strong association with AML with the inv(16) cytogenetic abnormality. The cells were not increased in chronic myelogenous leukemia (CML) and rarely increased in non-CML myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). Immunohistochemical staining of cases with increased CD1c(+) MDCs did not reveal clustering of the cells unlike that observed with myeloid neoplasms associated with increased plasmacytoid dendritic cells. Our findings indicate CD1c(+) MDC elevations are not uncommon in myeloid leukemias and are associated with CMML and AML, particularly AML with inv(16). © 2015 International Clinical Cytometry Society.

CD177 expression on neutrophils: in search of a clonal assay for myeloid neoplasia by flow cytometry.

OBJECTIVES: To determine whether the fraction of CD177+ neutrophils might be altered in clonal myeloid disorders, similar to the skewed κ/λ ratio for B-cell lymphomas, and could be used to identify myeloid neoplasms. METHODS: Blood and bone marrow samples were evaluated for the fraction of CD177+ neutrophils by flow cytometry. RESULTS: Skewed high neutrophil CD177(%) was not associated with neoplasia, but skewed low neutrophil CD177(%) was highly correlated with clonal myeloid disorders at values less than 40%. Specificity of low neutrophil CD177(%) for clonal myeloid disorders was 87% with a 40% cutoff and 95% with a 30% cutoff. Findings were most pronounced for myelodysplasia, with 52% (11/21) containing fewer than 40% CD177+ neutrophils. Specificity was also suggested by normalization of neutrophil CD177(%) in four patients who reached morphologic remission after therapy for myelodysplasia or acute leukemia. CONCLUSIONS: Skewed low neutrophil CD177(%) is highly associated with clonal myeloid disorders, particularly myelodysplasia, and may be useful for detecting clonal myeloid disorders.

NRP-1/CD304 expression in acute leukemia: a potential marker for minimal residual disease detection in precursor B-cell acute lymphoblastic leukemia.

Neuropilin-1 (NRP-1)/CD304 is a marker for plasmacytoid dendritic cells. We determined the distribution of NRP-1/CD304 expression on normal hematopoietic cells and in 167 acute leukemias by flow cytometry. NRP-1/CD304 surface expression was frequent in precursor B-cell acute lymphoblastic leukemia (36/51 [71%]) and uncommon in acute myeloid leukemia (22.9%). In acute myeloid leukemia, expression was noted in all (4/4) acute myeloid leukemias with the M4eo subtype and in 50% of specimens (6/12) with complex cytogenetics. On hematopoietic cells, NRP-1/CD304 was expressed on normal erythroid progenitors, plasma cells, and B-cell progenitors, as well as plasmacytoid dendritic cells. Expression was not consistently detected on other hematopoietic cell types. Owing to this distribution of expression, the detection of NRP-1/CD304 alone on a hematopoietic cell cannot be used to determine plasmacytoid dendritic cell differentiation. Finally, we show that NRP-1/CD304 is overexpressed in 30% of precursor B-cell acute lymphoblastic leukemia samples compared with normal B-cell progenitors, allowing for its potential use as a marker for the detection of minimal residual disease.

Bimodal cell populations are common in chronic lymphocytic leukemia but do not impact overall survival.

Flow cytometric histograms were evaluated for bimodal antigen expression on samples from 246 patients diagnosed with chronic lymphocytic leukemia (CLL) at University Hospitals of Cleveland, Cleveland, OH. Survival data were obtained, and the clinical significance of bimodality was evaluated using the Kaplan-Meier method and the log-rank test. Bimodal antigen expression was found in 107 cases (43.5%). CD38 and CD13 were the most common antigens to demonstrate bimodality at 14.5% and 12.9%, respectively, and CD20, CD11c, CD5, FMC-7, and surface immunoglobulin also were frequently bimodal. Bimodal antigen expression, the number of bimodal antigens, and bimodality of a specific antigen were not associated with decreased survival in patients with CLL, although bimodality for CD38 trended toward worse overall survival. Therefore, although bimodal antigen expression is common in CLL, the presence of bimodality does not seem to have significant prognostic importance

Diminished expression of CD19 in B-cell lymphomas.

BACKGROUND: CD19 is expressed on most B-cell lymphomas; however, the frequency and types of B-cell lymphomas with low-level expression of CD19 are not well characterized. METHODS: We reviewed flow cytometric histograms specifically for decreased CD19 expression on 349 cases analyzed by the Flow Cytometry Laboratory at University Hospitals of Cleveland (Cleveland, Ohio). Results of flow cytometry were correlated with the morphologic diagnosis. RESULTS: Of the cases reviewed, 125 (36%) showed a visible decrease in CD19 expression compared with normal B lymphocytes. Decreased CD19 expression was noted in 79% of follicular lymphomas (27 of 34), 36% of small lymphocytic lymphomas/chronic lymphocytic leukemias (82 of 228), 31% of mantle cell lymphomas (4 of 13), 24% of diffuse large B-cell lymphomas (8 of 33), and 13% of marginal zone B-cell lymphomas/lymphoplasmacytoid lymphomas (4 of 30) and was not observed in any Burkitt lymphoma (0 of 5) or hairy cell leukemia (0 of 6). Decreased CD19 expression was significantly more frequent in follicular lymphomas than in other lymphoma subtypes (P < 0.001). No significant difference was observed in the frequency of decreased CD19 expression based on histologic grade of follicular lymphoma. CONCLUSIONS: Diminished expression of CD19 expression occurs frequently in B-cell lymphomas, in particular follicular lymphoma, and may be helpful in identifying B-cell lymphoma cells in complex cell mixtures such as bone marrow specimens.