Eilatin: A novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph⁺) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-α (IFN-α) and cytosine arabinoside (Ara-C). Eilatin, IFN-α, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10^-7 and 1^0-6 M), IFN-α (500 U/mL), or Ara-C (10^-9 M and 10^-8 M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34⁺ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10^-7 M, IFN-α 500 U/mL, Ara-C 10^-9 M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34⁺ cells. All five patients were 100% Ph⁺ at diagnosis. BCR/ABL translocations were detected in 94.6 ± 0.6% of CD34⁺ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34⁺ cells for 16 hours to Eilatin 10^-7 M, IFN-α 500 U/mL, or Ara-C 10^-9 M were 54.5 ± 5%, 63.6 ± 5%, and 70 ± 4%, respectively (mean ± SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph⁺ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.