Diagnostic and prognostic value of DNA image cytometry in myelodysplasia.

Abstract

SUMMARY The DNA content of erythropoietic cells from 10 patients with refractory anaemia (RA) with megaloblastic changes, who subsequently developed acute non-lymphoblastic leukaemia (ANL), and from seven patients with megaloblastic marrow aspirates due to pernicious anaemia were compared by DNA image cytometry. The DNA distribution, the rate of aneuploid cells exceeding 5c (5cER), and the square deviation index of DNA values from the normal 2c-peak (2cDI) were recorded. Both variables were of diagnostic and prognostic importance for epithelial tumours, malignant lymphomas, and dysplastic lesions. A rate of 5cER>0 was found in eight of 10 myelodysplastic, but in none of seven control cases. Hypodiploidy was equally pronounced in both groups of patients. The 5cE had the highest discriminative value of all variables calculated. The 2cDI was not significantly different in either group. In pernicious anaemia the 2cDI depended mainly on the percentage of S cells, reflecting the defect of DNA synthesis. In RA with megaloblastosis the 2cDI correlated with the percentage of G2 cells, reflecting G2 arrest. In the myelodysplastic group the 2cDI correlated positively with the length oftime until ANL developed, indicating the prognostic relevance of 2cDI. Our findings show that in megaloblastic anaemia DNA image cytometry can distinguish myelodysplasia from pernicious anaemia and that it also provides prognostic information.Myelodysplastic syndromes (MDS) comprise a range of conditions which vary in their degree of risk of transformation to "overt" acute non-lymphoblastic leukaemia (ANL).' In clinical practice diagnosis and classification of MDS are mainly based on a wide range of morphological features,24 but the predictive value of morphological features for risk of transformation to ANL is controversial. Moreover, discrimination between MDS and reactive changes is not always possible.' While it has been shown with cytogenetic methods that MDS are usually clonal,7'0 such methods fail to detect small clones of low mitotic activity.

DNA image cytometry in MDS bone marrow smears

“…However, the most frequent method used in haematological material, by means of the nuclear DNA content, is still FCM (Barlogie et al, 1987;Montecucco et al, 1983;Clark et al, 1986;Peters et al, 1986;Hoy et al, 1989;Hiddemann et al, 1986;Look et al, 1985;Alanen et al, 1993;Parikh et al, 1995;Vidriales et al, 1995;Kamihira et al, 1994), which makes the results difficult to interprete due to an average of all lineages and maturation stages in the bone marrow. In contrast, ICM enables studies of intact single subpopulations of cells selected by morphology, both for prospective as well as for retrospective purpose (Auffermann et al, 1988;Bauer et al, 1990;Kropff et al, 1991;Muller et al, 1991;Widell et al, 1993c;Czader et al, 1993).…”

DNA content of granulocytes, monocytes, and lymphocytes in the bone marrow smears of patients with myelodysplastic syndromes

“…Non-clonal hematopoietic progenitor cell population in peripheral blood [7] as well as polyclonal or clonal hematopoiesis in bone marrows [11] of MDS has been reported. However, there are still, as far as we know, only a few studies of subpopulations of bone marrow cells in leukemias by modern ICM which combine the DNA content in individual cell types with their morphology [12,13,16,17,22,43]. Our observations of DNA hypodiploid lymphocytes is intriguing.…”

DNA ploidy analysis in histopathology

“…Next to the ploidy histogram evaluation criteria mentioned above for FCM, specific ICM DNA histogram criteria are the Auer ploidy classes (Figure 2), 9 Boecking's malignancy index, 10 entropy, 11 the 2C deviation index and the 5c‐exceeding rate (5cER) 12 . Certain authors define a tumour as aneuploid if the ICM‐obtained DNA histogram shows one single cell with a 5cER DNA content.…”