M. Einat et al., EILATIN - A NOVEL MARINE ALKALOID INHIBITS IN-VITRO PROLIFERATION OF PROGENITOR CELLS IN CHRONIC MYELOID-LEUKEMIA PATIENTS, Experimental hematology, 23(14), 1995, pp. 1439-1444
We examined the effect of Eilatin, a novel marine product, on the surv
ival of human myeloid progenitor cells (CFU-C) isolated from normal in
dividuals 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-f
orming units from bone marrow (BM) of seven CML patients in chronic ph
ase 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 statistica
lly 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-alp
ha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the abi
lity of the cells to proliferate in liquid culture and a reduction in
CFU-C content. Using fluorescent in situ hybridization (FISH), we eval
uated detection of the BCR/ABL fusion product in the CD34(+) cells. Al
l five patients were 100% Ph(+) at diagnosis. BCR/ABL translocations w
ere 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., h
as 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 marr
ow transplantation.