PMID- 11234892
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20171116
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 7
IP  - 2
DP  - 2001 Feb
TI  - Retinoid receptor expression and its correlation to retinoid sensitivity in 
      non-M3 acute myeloid leukemia blast cells.
PG  - 367-73
AB  - All-trans-retinoic acid (ATRA) has significantly improved the treatment results 
      in acute promyelocytic leukemia (M3). In non-M3 acute myeloid leukemia (AML), the 
      effects are less clear, and there is a pronounced heterogeneity in the 
      sensitivity to the growth-inhibitory effects of retinoids in leukemic cells from 
      different non-M3 AML patients. Retinoids exert their effects through a number of 
      nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors 
      (RXRs)]. In this study, we determined the expression of RAR alpha, RAR beta, RAR 
      gamma, and RXR alpha by real-time PCR in four cell lines and in blast cells from 
      patients with non-M3 AML before and after ATRA incubation. All four receptors 
      were expressed in cells from all 18 tested patient samples and in four myeloid 
      cell lines. In the majority of the patient samples as well as in the cell lines, 
      there was a pattern of high expression of RAR alpha and RXR alpha and low 
      expression of RAR beta and RAR gamma. There was no correlation between the basal 
      expression of any of the retinoid receptors and sensitivity to ATRA. A 24-h 
      exposure to ATRA increased the expression of RAR alpha, RAR beta, RAR gamma, and 
      RXR alpha in 46%, 77%, 30%, and 38% of the samples, respectively. The mean 
      increase in receptor expression was most pronounced for RAR beta and RXR alpha. 
      There was a significant correlation between an increase in RAR beta expression in 
      response to ATRA and sensitivity to ATRA (P < 0.014). No such correlations were 
      found for RAR alpha, RAR gamma, and RXR alpha. The expression of the monocytoid 
      marker CD14 was significantly correlated with increased expression of RAR alpha 
      (P = 0.03). We conclude that RAR alpha, RAR beta, RAR gamma, and RXR alpha are 
      expressed in non-M3 AML blast cells and that ATRA-induced expression of RAR beta 
      may be a marker for retinoid sensitivity.
FAU - Lehmann, S
AU  - Lehmann S
AD  - Department of Hematology, Karolinska Institute, Huddinge Hospital, Stockholm, 
      Sweden. Soren.Lehmann@medhs.ki.se
FAU - Paul, C
AU  - Paul C
FAU - Torma, H
AU  - Torma H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA Primers)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Division/drug effects
MH  - Cell Transformation, Neoplastic/drug effects
MH  - DNA Primers/chemistry
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Leukemia, Promyelocytic, Acute/drug therapy/genetics/*metabolism
MH  - Lipopolysaccharide Receptors/metabolism
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Retinoic Acid/biosynthesis/*genetics
MH  - Transcription, Genetic/drug effects
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured/*drug effects
EDAT- 2001/03/10 10:00
MHDA- 2001/06/19 10:01
CRDT- 2001/03/10 10:00
PHST- 2001/03/10 10:00 [pubmed]
PHST- 2001/06/19 10:01 [medline]
PHST- 2001/03/10 10:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2001 Feb;7(2):367-73.