Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation.

We sought to understand the genesis of the t(9;22) by characterizing genomic breakpoints in chronic myeloid leukemia (CML) and BCR-ABL-positive acute lymphoblastic leukemia (ALL). BCR-ABL breakpoints were identified in p190 ALL (n=25), p210 ALL (n=25) and p210 CML (n=32); reciprocal breakpoints were identified in 54 cases. No evidence for significant clustering and no association with sequence motifs was found except for a breakpoint deficit in repeat regions within BCR for p210 cases.

Effects of Flt3 ligand and interleukin-7 on in vitro growth of acute lymphoblastic leukemia cells.

We investigated the effects of Flt3/Flk-2 ligand (FL) and interleukin-7 (IL-7) on DNA synthesis and proliferation of blast cells from patients with acute lymphoblastic leukemia (ALL). After 7 days of serum-free suspension culture of 19 samples, FL induced maximal DNA synthesis in two cases, whereas the combination of FL and IL-7 did so in another eight samples with a stimulation index (SI) >2. However, the number of viable cells after 7 days of liquid culture decreased in all but one sample.

The role of marrow accessory cell populations in the augmentation of human erythroid progenitor cell (BFU-E) proliferation by prostaglandin E.

The requirement for CD8+ T lymphocytes in the stimulation of erythroid progenitor cells by prostaglandin E (PGE) was examined. When low density bone marrow (LD-BM) or non-adherent bone marrow (NA-BM) cells were depleted of CD8+ cells the enhancing effect of PGE on BFU-E proliferation was abrogated. However, further enrichment of marrow progenitor cells by depletion of accessory cells using a cocktail of specific monoclonal antibodies, immunoadherence and fluorescence activated cell sorting with the MY10 monoclonal antibody resulted in a population of erythroid progenitor cells which were responsive to the enhancing effect of PGE despite the absence of CD8+ cells.