CD7 x Tubulin

Human primary myeloma cells are well known to be heterogeneous with regard to morphology and surface phenotype. We confirmed the heterogeneous expression of such multilineage markers as CD33, CD7, CD56, CD4, and CD86 in primary myeloma cells from 20 patients with multiple myeloma and in 8 human myeloma cell lines. CD33 expression in the Liu01 cell line, a subclone of U266 cells, and in vitamin D3-treated ILKM3 cells, correlated with a monocytoid morphology featuring convoluted nuclei and with increased C/EBPalpha expression. CD56+ myeloma cells from some myeloma patients and the CD56+ (but not the CD56-) myeloma cell lines expressed neuronal cell markers, such as neuron-specific enolase and beta-tubulin III. CD7 expression in Liu01 cells and forskolin-stimulated U266 cells coincided with the presence of large cytoplasmic granules, and these cells featured increased expression of perforin messenger RNA and significant natural killer cell activity. Interleukin 6 (IL-6), a growth factor for myeloma cells, down-regulated CD33, CD7, or CD56 expression in primary myeloma cells, as well as in Liu01 cells. Therefore, these data suggest that human myeloma cells are capable of inducing the expression of multilineage markers and that IL-6 can down-regulate such expression.

We describe a unique case of adult T-cell leukemia/lymphoma (ATL). The patient had typical clinicohematological features as ATL, but showed a lack of antibody to human T-cell leukemia virus type-1 (HTLV-1) and was negative for HTLV-1 proviral DNA in the peripheral mononuclear cells by means of polymerase chain reaction. The phenotype of tumor cells revealed CD7+, CD5+, CD2+, CD3+, WT31-, TcR delta 1-, CD4-, CD8-, CD25-, and the karyotype showed a 5q-, t(12;18). HTLV-1 unrelated ATL is very rare, and the karyotype as in our case has not been reported previously.

The endogenous metabolite, 2-methoxyestradiol (2ME), is an inhibitor of tubulin polymerization and is therefore toxic to dividing fast-growing tumor cells. Transformed cells are not equally susceptible to the effects of 2ME. In this study the effects of 1-2 microM doses of 2ME on cell cycle progression, apoptosis induction and on p53 levels were evaluated using flow cytometry in cells with different p53 status. No effect of 2ME was seen in normal human skin fibroblast strain HSF43 with wild-type (wt) p53. However, in SV40 T antigen transformed HSF43 cells (line E8T4), 2ME caused a prominent G2/M arrest, with subsequent micronuclei formation followed by apoptosis. Increased p53 levels were present in the G2/M cells. Our results suggest that 2ME, being a microtubule poison, may release the bound p53 from T antigen, and that this p53 may enhance the apoptotic effects. Two lymphoblast cell lines derived from the same donor, TK6, expressing low levels of wt p53, and WTK1, expressing high levels of mutant p53, showed similar moderate responses to 2ME at 37 degrees C. The effects included enhanced apoptosis and a modest G2/M block. No increase in p53 levels was seen. However, at the permissive temperature of 30 degrees C marked increases in apoptosis and a prominent G2/M-phase block, similar to that seen in the E8T4 cells, were present in the WTK1 cells, indicating that the high levels of mutant p53 have now become functional, enhancing the apoptotic effects initiated by 2ME.