Flow cytometry enables multiparametric characterization of hematopoietic cell immunophenotype. Deviations from normal immunophenotypic patterns comprise a cardinal feature of many hematopoietic neoplasms, underscoring the ongoing essentiality of flow cytometry as a diagnostic tool. However, understanding of aberrant hematopoiesis requires an equal understanding of normal hematopoiesis as a comparator. In this review, we outline key features of healthy adult hematopoiesis and lineage specification as illuminated by flow cytometry and provide diagrams illustrating what a diagnostician may observe in flow cytometric plots. These features provide a profile of baseline hematopoiesis, to which clinical samples with suspected neoplasia may be compared.
Flow cytometry provides multiparametric, single-cell immunophenotypic profiles of hematopoietic cells.
Familiarity with the immunophenotypic profile of healthy bone marrow is essential for understanding aberrancies that arise with hematologic malignancies.
Flow cytometry correlates well with the molecular features of human hematopoiesis and can provide clinically tractable markers for lineage and differentiation state.
After birth, nearly all hematopoietic cells in humans are produced within the bone marrow. Detailed characterization of bone marrow hematopoiesis can therefore provide significant insight into the function (or dysfunction) of a patient’s blood-forming system. Flow cytometry provides a clinically tractable, multiparametric approach to determine the immunophenotypic characteristics of hematopoietic cells. The resulting profile can highlight abnormalities in the differentiation or maturation of bone marrow elements, which has proven particularly useful in the diagnosis of hematologic malignancies. Despite the advent of transcriptional and proteomic technologies providing ever-deeper characterization of the biology of hematopoiesis, flow cytometry remains the clinical standard for immunophenotypic diagnosis. However, any actionable understanding of hematopoietic dysfunction requires an equal understanding of healthy hematopoiesis, providing a baseline from which the diseased marrow diverges.
Here, we provide a brief review of the current understanding of normal hematopoiesis in the healthy human bone marrow as characterized by flow cytometry. We also explore the immunophenotypic changes associated with lineage specification and differentiation in humans, which can differ significantly from well-studied murine models. We use illustrative diagrams modeling normal patterns of maturation to illustrate concisely the patterns a diagnostician may see in flow cytometry plots. These examples should provide a guide for the phenotypic assessment of hematopoietic stem cells, lineage precursors, and maturing lineage-defined cells. From a clear picture of healthy hematopoiesis, diagnosticians may more easily make comparisons with clinical samples and render accurate flow cytometric diagnoses for hematologic disorders.