Heterogeneity of cultured leukemic lymphoid progenitor cells from B cell precursor acute lymphoblastic leukemia (ALL) patients.

Abstract

Colony assays were performed for 50 patients with B cell precursor acute lymphoblastic leukemia (ALL). Blast colony formation was observed for 33 patients, and the plating efficiency (PE) showed a marked interpatient variation, which indicates a pronounced biological heterogeneity at the level of leukemic progenitor cells. Notably, the mean PE of leukemic B cell precursors from patients with a pseudodiploid or near-diploid karyotype with structural chromosomal abnormalities (SCA) was significantly higher than the mean PE of normal diploid or hyperdiploid cases. All patients who had SCA involving 7p13, 11q23-24, or 12pll-13, and patients with a Philadelphia chromosome had high PE values. The S phase percentage, expression of CD19 antigen, and relapse status were also correlated with PE. Significantly, colony blasts had slightly different surface marker profiles in each case and were common ALL antigen negative in 33% of cases, which indicates the existence of a marked immunological heterogeneity at the level of leukemic progenitor cells.

Antigen-independent regulation of cytoplasmic calcium in B cells with a 12-kDa B-cell growth factor and anti-CD19.

“…Importantly, B-lineage lymphoid progenitor cells form B-cell precursor colonies in an in vitro assay system that was recently described (24,33,35,36). When tested for biological effects on B-lineage lymphoid progenitor cells in 17 cases (Table 1), anti-CD19 mAb B43 induced proliferation and B-cell precursor colony formation in 3 cases and augmented spontaneous colony formation in 4 cases.…”

“…When tested for biological effects on B-lineage lymphoid progenitor cells in 17 cases (Table 1), anti-CD19 mAb B43 induced proliferation and B-cell precursor colony formation in 3 cases and augmented spontaneous colony formation in 4 cases. Hence, while 14/17 1091 24-2804 Highly blast-enriched fresh B-cell precursor ALL marrow samples were cultured in the presence of purified LMW-BCGF (2 ng/ml) and affinity-purified mAb B43 at various concentrations and were assayed for blast colony formation as described (33,35,36). Detailed immunological analyses on B-cell precursor colony cells were performed to determine whether the LMW-BCGF or anti-CD19 mAb B43 signals induce differentiation in B-cell precursors.…”

“…LMW-BCGF (12-kD; a) preparations did not contain detectable amounts of IL-1, IL-2, IL-3, GM-CSF, G-CSF, or y interferon as determined by standard bioassays, but they were able to induce proliferation of sIg-activated B cells, with a maximal stimulation index of 23 B-Cell Precursor Colony ,Assay. Leukemic B-cell precursors from patients were assayed for colony formation in vitro by using a B-cell precursor colony assay system as previously described (35,36). Leukemic B-cell precursor blasts were suspended in a minimal essential medium (GIBCO) supplemented with 0.9% methylcellulose, 30%6 calf serum, 1% penicillin/streptomycin, and various concentrations of LMW-BCGF, B43 (anti-CD19), and BA-5 (anti-HMW-BCGF receptor).…”

“…On day 7, colonies containing >20 cells were counted on a grid by using an inverted phase-contrast microscope with high optical resolution. Subsequently, colonies were harvested, and morphological, immunological, and cytogenetic features of colony cells were analyzed as described (36). [Ca2+]i identical to that of control cells (Fig.…”

Hypermethylation of the spleen tyrosine kinase promoter in T-lineage acute lymphoblastic leukemia

“…Mononuclear cell fractions containing >95% leukemic cells were isolated by centrifugation on Ficoll-Hypaque density gradients (Uckun et al, 1985(Uckun et al, , 1997. Diagnosis of T-lineage ALL was based on morphological, biochemical and immunological features of the (Uckun et al, 1989(Uckun et al, , 1997. Control samples also included one pediatric thymus.…”