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

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-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, 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-alpha (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-alpha 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-alpha 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.

• Authors: M Einat, M Lishner, A Amiel, A Nagler, S Yarkorli, A Rudi, Y Kashman, D Markel, I Fabian
• Journal: Experimental hematology (Exp Hematol) Vol. 23 Issue 14 Pg. 1439-44 (Dec 1995) ISSN: 0301-472X [Print] Netherlands
• PMID: 8542929 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD34
• Antineoplastic Agents
• Interferon-alpha
• Phenanthrolines
• Cytarabine
• eilatine

Topics

• Adolescent
• Adult
• Antigens, CD34 (analysis)
• Antineoplastic Agents (chemistry, pharmacology)
• Bone Marrow (pathology)
• Cell Division (drug effects)
• Cell Survival (drug effects)
• Child
• Child, Preschool
• Cytarabine (pharmacology)
• Female
• Hematopoietic Stem Cells (pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Interferon-alpha (pharmacology)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology)
• Male
• Phenanthrolines (chemistry, pharmacology)
• Tumor Cells, Cultured