Potent Antileukemic Activity of the Novel Agents Norsegoline and Dibezine

Michal Einat, Ina Fabian*, Yoel Kashman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the effect of norsegoline, a natural marine product, and dibezine, a synthetic product, on the survival of human myeloid progenitor cells [colony-forming unit-cells (CFU-C)] from normal individuals and from 10 patients with Philadelphia-positive chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared their effect to the effect of IFN-α. Norsegoline, dibezine, and IFN-α inhibited the proliferation of CFU-C in a dose-dependent manner. The number of CFU-C from bone marrow (BM) of five CML patients in chronic phase exposed for 16 h to norsegoline (10-8-10-6 m), dibezine (10-8-10-6 m), and IFN-α (500 units/ml) was found to be statistically lower (P < 0.05) than the number of CFU-C derived from normal individuals. A 16-h drug exposure of CD34+ cells isolated from the peripheral blood of three CML patients in blastic crisis and from BM of two patients in chronic phase resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using the fluorescent in situ hybridization technique, we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Philadelphia positive at diagnosis. BCR/ABL translocations were detected in 94.6 ± 0.6% of cells following their growth in liquid culture for 7 days. Following exposure of CD34+ cells to norsegoline, dibezine, or IFN-α, BCR/ABL fusion signals could be detected in 73 ± 11%, 66.5 ± 4.7%, and 66.0 ± 2.5% of cells from BM and 72.3 ± 5%, 68.8 ± 7%, and 60.6 ± 6.8% of peripheral blood, respectively. Our data indicate that norsegoline and dibezine have in vitro an antileukemic effect against Philadelphia-positive cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or peripheral blood of CML patients in conjunction with autologous bone marrow transplantation.

Original languageEnglish
Pages (from-to)823-829
Number of pages7
JournalClinical Cancer Research
Volume1
Issue number8
StatePublished - 1 Aug 1995

Fingerprint

Dive into the research topics of 'Potent Antileukemic Activity of the Novel Agents Norsegoline and Dibezine'. Together they form a unique fingerprint.

Cite this