PMID: 9172997Jan 1, 1997Paper

Apoptotic and antiproliferative effects of gemcitabine and gemcitabine plus Ara-C on blast cells from patients with blast crisis chronic myeloproliferative disorders

Haematologica
V SantiniP R Ferrini

Abstract

Blast phase of chronic myeloid leukemia (CML) as well as the rare acute transformation of other chronic myeloproliferative disorders constitute forms of leukemia that are particularly refractory, even to aggressive chemotherapy. Many attempts have thus been made to identify new drugs that could be active in these diseases. We wanted to evaluate whether gemcitabine (dFdC), a pyrimidine analogue widely employed in lung cancer chemotherapy, was able to block in vitro proliferation of bcr/abl-positive and bcr/abl-negative blast cells in primary culture. We already showed that gemcitabine is active in inhibiting proliferation and inducing apoptosis of HL60 cells. We studied the influence of dFdC on the proliferative potential of blasts by means of tritiated thymidine uptake, colony formation in semisolid medium and cell cycle parameters at flow cytometry. The efficacy of dFdC in inducing apoptosis was evaluated by flow cytometry (A0 peak) and by DNA agarose gel electrophoresis. We demonstrated that dFdC already inhibits tritiated thymidine uptake at doses of 10 microM after 72 hours of culture, and that this effect is dose dependent. The addition of Ara-C 5 microM in the culture medium of dFdC provoked a synergistic inhibitory effec...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis