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

M. Einat, M. Lishner, A. Amiel, A. Nagler, S. Yarkorli, A. Rudi, Y. Kashman, D. Markel, I. Fabian

Research output: Contribution to journalArticlepeer-review

Abstract

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 10-6 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.

Original languageEnglish
Pages (from-to)1439-1444
Number of pages6
JournalExperimental Hematology
Volume23
Issue number14
StatePublished - 1995

Keywords

  • Alkaloid
  • CML
  • Eilatin

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