The potential of proliferative and apoptotic parameters in clinical flow cytometry of myeloid malignancies

Abstract

Standardization of the detection and quantification of leukocyte differentiation markers by the EuroFlow Consortium has led to a major step forward in the integration of flow cytometry into classification of leukemia and lymphoma. In our opinion, this now enables introduction of markers for more dynamic parameters, such as proliferative and (anti)apoptotic markers, which have proven their value in the field of histopathology in the diagnostic process of solid tumors and lymphoma. Although use of proliferative and (anti)apoptotic markers as objective parameters in the diagnostic process of myeloid malignancies was studied in the past decades, this did not result in the incorporation of these biomarkers into clinical diagnosis. This review addresses the potential of these markers for implementation in the current, state-of-the-art multiparameter analysis of myeloid malignancies. The reviewed studies clearly recognize the importance of proliferation and apoptotic mechanisms in the pathogenesis of bone marrow (BM) malignancies. The literature is, however, contradictory on the role of these processes in myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasms, and acute myeloid leukemia. Furthermore, several studies underline the need for the analysis of the proliferative and apoptotic rates in subsets of hematopoietic BM cell lineages and argue that these results can have diagnostic and prognostic value in patients with myeloid malignancies. Recent developments in multiparameter flow cytometry now allow quantification of proliferative and (anti)apoptotic indicators in myeloid cells during their different maturation stages of separate hematopoietic cell lineages. This will lead to a better understanding of the biology and pathogenesis of these malignancies.

Flow cytometric analysis of myelodysplasia: Pre‐analytical and technical issues—Recommendations from the European LeukemiaNet

“…Notably, the markers recommended only identify those that have been validated in a multicenter setting. Several studies have introduced markers that may be of additive value, either as a single marker, in combination with a diagnostic mini‐panel or in combination with other markers (Alayed et al, 2020 ; Della Porta et al, 2012 ; Mestrum et al, 2021 ; Shameli et al, 2020 ).…”

Proliferative and anti‐apoptotic fractions in maturing hematopoietic cell lineages and their role in homeostasis of normal bone marrow

“…Effects of treatment modalities for myeloid malignancies can be predicted based on the proliferative and anti‐apoptotic capacity in the different hematopoietic cell lineages [11]. Erythroblasts are found to be highly proliferative and, hence, therapies that counter‐act on proliferating cells (e.g.…”

“…The potential of proliferative and apoptotic markers in establishing a better prognosis and prediction of treatment response in myeloid malignancies was studied in the past decades [11], but this did not lead to the incorporation of the intracellular dynamic markers in the diagnostic work-up of these malignancies. The number of parameters that could be analyzed by histopathological and flow cytometric analyses was limited at the time that these markers were initially studied.…”

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“…Annexin V/FITC assay estimates the number of cells that undergo apoptosis. This method discriminate to discrimination between viable, apoptosis, and necrotic cells 31 . When individual drugs were evaluated for % of apoptotic cells, it was observed that at 24 and 48 hrs the number of apoptotic cells was more compared to the control cells.…”