TY - JOUR
T1 - Inhibition by retinoic acid of myeloid progenitors in chronic myeloid leukemia and myeloproliferative disease
T2 - Increased sensitivity in blastic phase of chronic myeloid leukemia
AU - Januszewicz, Elchanan
AU - Rabizadah, Esther
AU - Maimon, Zipora
AU - Zaizov, Rina
AU - Shaklai, Matityahu
N1 - Funding Information:
ACKNOWLEDGEMENWTeS w ould like to acknowledge the assistance of Professor M. Djaldetti in accruing patients and the assistance of Joan Osbourne and Sandra De Vincenti in typing the manuscript. This work was supported by grants from the Moise and Freda Eskanasy Fund of the Cancer Institute, Tel Aviv University, and the Israel Cancer Research Fund.
PY - 1988/1
Y1 - 1988/1
N2 - The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 ±9% (SEM) of control at 0.3 μM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 ± 12% CML chronic phase, 58 ± 26% MPD at 3.0 μM RA). At 0.3 μM and 1.0 μM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p < 0.02 and p < 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progmitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 ± 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.
AB - The effects of all-trans retinoic acid (RA) were tested on the growth in vitro of myeloid progenitors from peripheral blood or bone marrow, in 25 patients with chronic myeloid leukemia (CML), ten of whom were either in accelerated or blastic phase, and in nine patients with myeloproliferative disease (MPD). The responses were compared with 12 normal bone marrow controls obtained from patients with lymphoma. Clonal growth in CML blastic and accelerated phase was inhibited to the greatest degree (mean 49 ±9% (SEM) of control at 0.3 μM RA). The responses in CML chronic phase and MPD were more heterogeneous, but significant inhibition was seen at higher concentrations of RA (50 ± 12% CML chronic phase, 58 ± 26% MPD at 3.0 μM RA). At 0.3 μM and 1.0 μM RA there were significant differences between the CML chronic phase and the CML blastic phase patients (p < 0.02 and p < 0.05 respectively). At these concentrations there was no significant inhibition on normal bone marrow myeloid progmitors. Inhibition was independent of the proportions of progenitors in S phase, as assessed by tritiated thymidine suicide. Preincubation of cells from selected patients with RA for 48 hours before culture in agar resulted in a significant degree of inhibition (48 ± 8% of control). Inhibition was prevented by delaying the addition of RA from 24 to 48 hours from the beginning of the culture, indicating that RA exerts an early direct effect on myeloid progenitors.
KW - CFU-GM
KW - Chronic myeloid leukemia
KW - Myeloproliferative disease
KW - Retinoic acid
UR - http://www.scopus.com/inward/record.url?scp=0023870710&partnerID=8YFLogxK
U2 - 10.3109/00313028809085187
DO - 10.3109/00313028809085187
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AN - SCOPUS:0023870710
SN - 0031-3025
VL - 20
SP - 1
EP - 6
JO - Pathology
JF - Pathology
IS - 1
ER -
