ABSTRACT
Myeloid malignancies showing CD141+ myeloid dendritic cell (MDC) differentiation have not been documented. Here, we describe a patient with juvenile myelomonocytic leukemia in which a prominent CD141+ cell population was identified most consistent with CD141+ MDCs based on phenotypic similarity with normal CD141+ MDCs. Molecular studies demonstrated a KRAS mutation. The findings from the spleen and bone marrow are described. This is the first well-documented demonstration of CD141+ MDC differentiation of a hematopoietic neoplasm.
Subject(s)
Antigens, Surface/analysis , Biomarkers, Tumor/analysis , Cell Differentiation , Dendritic Cells/immunology , Leukemia, Myelomonocytic, Juvenile/immunology , Antigens, CD1/analysis , Biomarkers, Tumor/genetics , Biopsy , CD13 Antigens/analysis , Child , Dendritic Cells/pathology , Flow Cytometry , Genetic Predisposition to Disease , Glycoproteins/analysis , Humans , Immunohistochemistry , Leukemia, Myelomonocytic, Juvenile/genetics , Leukemia, Myelomonocytic, Juvenile/pathology , Leukemia, Myelomonocytic, Juvenile/therapy , Male , Mutation , Phenotype , Proto-Oncogene Proteins p21(ras)/genetics , ThrombomodulinABSTRACT
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.
Subject(s)
Antigens, CD1/metabolism , Dendritic Cells/pathology , Glycoproteins/metabolism , Leukemia, Myeloid, Acute/pathology , Leukemia, Myelomonocytic, Chronic/pathology , Myeloid Cells/metabolism , Myeloproliferative Disorders/pathology , Flow Cytometry/methods , Humans , Immunohistochemistry/methods , Leukemia, Myelomonocytic, Chronic/diagnosis , Myelodysplastic Syndromes/pathology , Myeloid Cells/pathologyABSTRACT
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.
Subject(s)
Biological Assay , Flow Cytometry/methods , Isoantigens/metabolism , Myelodysplastic Syndromes/diagnosis , Neutrophils/pathology , Receptors, Cell Surface/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Bone Marrow Cells/pathology , Child , Child, Preschool , Clone Cells/pathology , Female , GPI-Linked Proteins/metabolism , Humans , Infant , Male , Middle Aged , Myelodysplastic Syndromes/metabolism , Neutrophils/metabolism , Sensitivity and Specificity , Young AdultABSTRACT
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.