Our data demonstrate immunophenotypic, cytogenetic, and molecular heterogeneity of NT-ALL and favorable prognosis of most NT-ALL across different immunophenotypic and/or genetic ALL subtypes.
Our results indicate that severe HHV-6 infection may induce reversible myelodysplastic changes. These findings contribute to elucidate the pathogenicity of HHV-6 and furthermore suggest that HHV-6 infection must also be considered as a cause of dysplasia in the differential diagnosis of MDS.
Indirubin-3'-monoxime (IO) is a derivative of Indirubin, compound of a Chinese medicinal recipe used to treat various diseases including leukemia. In this study, we investigated to what extent IO inhibits the growth of normal human lymphocytes. We defined various experimental conditions of peripheral blood lymphocyte treatment: IO introduced (i) on unstimulated lymphocytes, (ii) or on stimulated lymphocytes at the time of phytohemagglutinin stimulation (L1 protocol), (iii) 48 h after the beginning of stimulation (L2 protocol), and (iv) after nocodazole synchronization of stimulated lymphocytes. IO induces a concentration dependent cytotoxic effect yielding a characteristic sub-G1 peak in normal stimulated lymphocytes. Cell death was partly due to necrosis and apoptosis. Normal unstimulated lymphocytes remained insensitive to the cytotoxic effect of 10 microM IO treatment. A cell cycle inhibition was observed after IO treatment, stronger for the L1 than for the L2 protocol, without induction of polyploidy after Nocodazole synchronization. These cellular consequences were associated with a decrease in CDK activity, and with CDK and cyclin gene expression modifications. The inhibition of lymphocyte proliferation by IO indicates that indirubin derivatives may be potent immunosuppressive agents.
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