Aneuploidy and percentage of S-phase cells determined by flow cytometry correlate with cell phenotype in childhood acute leukemia

Abstract

Cellular DNA content distributions of propidium-iodide-stained bone marrow blasts were determined by flow cytometry (FCM) for 225 untreated children with acute leukemia and were correlated with leukemia cell phenotype and karyotype. Aneuploidy of the primary malignant stem line was detected in 54 cases (24%): 51 hyperdiploid and 3 hypodiploid. A second stem line with approximately twice the DNA content of the primary stem line was recognized by FCM in 28 cases (23 ALL, 5 ANLL) and may be an important source of leukemia cell heterogeneity. The degree of DNA content abnormality detected by FCM was highly correlated (r = 0.98) with the number of whole chromosome gains or losses in the leukemia karyotype. Aneuploidy detectable by FCM was more frequent in acute lymphoblastic leukemia (ALL) (52 of 173, 30.1%) than in acute nonlymphoblastic leukemia (2 of 52, 3.8%) (p less than 0.001). In the ALL group, aneuploidy was significantly correlated with the cell surface expression of common ALL antigen: 46 of 127 antigen-positive cases were aneuploid compared to 6 of 46 antigen-negative cases (p less than 0.003). Only 2 of 21 cases of T-cell ALL without common ALL antigen had detectable aneuploidy, which was significantly less than in the common ALL group (p = 0.02). The median percentage of cells in S- phase was significantly greater for B-cell and erythrocyte rosette- positive T-cell ALL, than for the other phenotypic subgroups. We conclude that aneuploidy and S-phase cell percentage are correlated with the state of leukemia cell differentiation. The biologic basis for the correlation is not established, but may be linked to the process of malignant transformation.

Differential expression of cell proliferation regulatory proteins in B‐ and T‐lineage acute lymphoblastic leukaemias

“…We found that the mean PCNA expression is significantly higher in T-ALL than in non-T-ALL, in line with the similar finding of Keim et al (1990). Nevertheless, one should bear in mind that both our series and Keim's did not contain mature B-ALL, known to have a very high proliferation activity (Look et al, 1982;Ffrench et al, 1987). The conclusion which could be drawn from this observation is that T-ALL cells divide more intensively than other immunological types (except mature B), in terms, for example, of the shortening of the duration of all cell-cycle phases.…”

“…When all T-lineage ALL cases are considered as one group, no difference was found for S or S+G2+M cells between T-cell lineage and B-cell (mature B-cell excluded) ALL (Ffrench et al, 1987). However, the percentage of bone marrow S-phase ALL blasts, determined as the 3 H-thymidine labelling index (Murphy et al, 1977;Dow et al 1982) or flow cytometry (Look et al, 1982) was higher in E(+) T-cell ALL when compared not only to B-lineage ALL (mature B-ALL excluded), but also to E(ÿ) T-lineage ALL. In order to study ALL blast proliferation status more precisely, we used PCNA and certain cdks and cyclins expression at the protein level.…”

Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA

“…Our survey adds a cautionary note to those seeking to predict survival of adults with ALL on DNA index alone. DNA index provides only a measure of ploidy without detailed knowledge of the more prognostically important structural change (Look et al, 1982;Smets et al, 1987). The hierarchical classification was more prognostically significant than the ploidy classification used alone, and only the hierarchical classification added prognostic significance to age, sex and WBC.…”

Sequential and hierarchical chromosomal changes and chromosome instability are distinct features of high hyperdiploid pediatric acute lymphoblastic leukemia

“…By the 1970s the hyperdiploid (HD) pre-B pediatric acute lymphoblastic leukemia (B-pALL), and by the mid 1980s even the high hyperdiploid (HeH) category was defined using conventional cytogenetic analysis (CCA) as well as DNA cytometry [1][2][3][4][5][6][7][8][9][10]. Later, based on treatment response, the low hyperdiploid (HeL) with modal number (MN) 47-50 and high hyperdiploid (MN 51-67) subgroups were distinguished, the latter of which is the most frequent (25-30%) subtype of B-pALL [11][12][13].…”