PMID- 8427982
OWN - NLM
STAT- MEDLINE
DCOM- 19930311
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 81
IP  - 4
DP  - 1993 Feb 15
TI  - 9-cis-retinoic acid: effects on normal and leukemic hematopoiesis in vitro.
PG  - 1009-16
AB  - Retinoic acid exhibits effects on the proliferation and differentiation of many 
      hematopoietic cells. Cellular responsiveness to retinoic acid (RA) is conferred 
      through two distinct classes of nuclear receptors, the RA receptors (RARs) and 
      the retinoid X receptors (RXRs). The RARs bind to both 9-cis- and all-trans-RAs, 
      but 9-cis-RA alone directly binds and activates RXR. This suggested that 9-cis-RA 
      could have expanded hematopoietic activities as compared with all-trans-RA. We 
      compared the abilities of 9-cis- and all-trans-RAs to induce differentiation and 
      inhibit proliferation of three acute myelogenous leukemia (AML) cell lines and 
      fresh leukemic cells from 28 patients and found that: (1) 9-cis-RA in general was 
      more potent than all-trans-RA in suppressing the clonal growth of two AML cell 
      lines and 17 AML samples from patients, including four from individuals with 
      acute promyelocytic leukemia (APL). Eleven leukemic samples, including three from 
      patients with chronic myelogenous or chronic myelomonocytic leukemia, were 
      relatively refractory to both retinoids. (2) The range of activities of both 
      retinoids was similar except that the clonal growth of samples from three AML 
      patients were inhibited by 9-cis-RA, but not by all-trans-RA. (3) Both retinoids 
      inhibited the clonal proliferation of leukemia cells without necessarily inducing 
      their differentiation; in fact, the only fresh AML cells that were able to 
      undergo differentiation were from patients with APL and one individual with M2 
      AML. (4) Both retinoids enhanced myeloid and erythroid clonal growth from normal 
      individuals, and 9-cis-RA showed slightly more stimulation of the myeloid clonal 
      growth than did the all-trans-RA. Our study suggests that 9-cis-RA is worthy of 
      further study for the treatment of selected individuals with AML.
FAU - Sakashita, A
AU  - Sakashita A
AD  - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
FAU - Kizaki, M
AU  - Kizaki M
FAU - Pakkala, S
AU  - Pakkala S
FAU - Schiller, G
AU  - Schiller G
FAU - Tsuruoka, N
AU  - Tsuruoka N
FAU - Tomosaki, R
AU  - Tomosaki R
FAU - Cameron, J F
AU  - Cameron JF
FAU - Dawson, M I
AU  - Dawson MI
FAU - Koeffler, H P
AU  - Koeffler HP
LA  - eng
GR  - CA26038/CA/NCI NIH HHS/United States
GR  - CA33936/CA/NCI NIH HHS/United States
GR  - CA42710/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Erythroid Precursor Cells/cytology/drug effects
MH  - Hematopoiesis/*drug effects
MH  - Hematopoietic Stem Cells/cytology/drug effects
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
MH  - Leukemia, Myeloid, Acute/*pathology
MH  - Leukemia, Promyelocytic, Acute/pathology
MH  - Stereoisomerism
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1993/02/15 00:00
MHDA- 1993/02/15 00:01
CRDT- 1993/02/15 00:00
PHST- 1993/02/15 00:00 [pubmed]
PHST- 1993/02/15 00:01 [medline]
PHST- 1993/02/15 00:00 [entrez]
AID - S0006-4971(20)85122-2 [pii]
PST - ppublish
SO  - Blood. 1993 Feb 15;81(4):1009-16.