PMID- 8193364
OWN - NLM
STAT- MEDLINE
DCOM- 19940627
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 83
IP  - 11
DP  - 1994 Jun 1
TI  - Novel retinoic acid, 9-cis retinoic acid, in combination with all-trans retinoic 
      acid is an effective inducer of differentiation of retinoic acid-resistant HL-60 
      cells.
PG  - 3289-97
AB  - Recent studies have shown that a high proportion of patients with acute 
      promyelocytic leukemia (APL) achieve complete remission after treatment with 
      all-trans retinoic acid (RA). Nevertheless, despite an initial good response, 
      most patients that received continuous treatment with all-trans RA relapse and 
      develop RA-resistant disease. The 9-cis RA is a high-affinity ligand for retinoid 
      X receptors (RXRs) and also binds efficiently to retinoic acid receptors (RARs); 
      all-trans RA is a ligand for RARs. Both alone are able to induce differentiation 
      of wild-type HL-60 cells. We found that neither all-trans RA nor 9-cis RA (< 2 x 
      10(-6) mol/L) induced differentiation of RA-resistant HL-60 cells into either 
      mature granulocytes or monocytes. However, morphologic differentiation of the 
      RA-resistant HL-60 cells was induced by 10(-6) mol/L all-trans RA combined with 
      various concentrations (10(-12) to 10(-6) mol/L) of 9-cis RA. Electron 
      microscopic examination also confirmed that the combination of both retinoids 
      induced RA-resistant HL-60 cells to differentiate to mature granulocytes. 
      Functional analysis of differentiation (NBT reduction activity) confirmed the 
      necessity of both analogs to induce differentiation. Also, expression of 
      myeloid-specific differentiation antigens (CD11b and CD14) as well as migration 
      inhibitory factor-related protein (MRP)-8/14 mRNAs were upregulated only in the 
      presence of both retinoids in a dose-dependent manner. In these conditions 
      3H-thymidine incorporation was inhibited and numbers of viable cells were 
      decreased, suggesting that all-trans RA with 9-cis RA may inhibit cell growth and 
      induce differentiation of RA-resistant HL-60 cells into mature granulocytes. 
      These studies suggest that 9-cis RA in combination with all-trans RA is an 
      effective inducer of RA-resistant HL-60 cells and may have implications for both 
      the biology of retinoids and clinical treatment of RA-resistant acute myelogenous 
      leukemia, including APL patients.
FAU - Kizaki, M
AU  - Kizaki M
AD  - Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
FAU - Nakajima, H
AU  - Nakajima H
FAU - Mori, S
AU  - Mori S
FAU - Koike, T
AU  - Koike T
FAU - Morikawa, M
AU  - Morikawa M
FAU - Ohta, M
AU  - Ohta M
FAU - Saito, M
AU  - Saito M
FAU - Koeffler, H P
AU  - Koeffler HP
FAU - Ikeda, Y
AU  - Ikeda Y
LA  - eng
GR  - CA33936/CA/NCI NIH HHS/United States
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  - 0 (Antigens, Differentiation)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Calgranulin A)
RN  - 0 (Calgranulin B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Antigens, Differentiation/genetics
MH  - Calcium-Binding Proteins/genetics
MH  - Calgranulin A
MH  - Calgranulin B
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Resistance
MH  - Humans
MH  - Leukemia, Promyelocytic, Acute/drug therapy/*pathology
MH  - RNA, Messenger/analysis
MH  - Receptors, Retinoic Acid/genetics
MH  - Stereoisomerism
MH  - Tretinoin/administration & dosage/*pharmacology/therapeutic use
MH  - Tumor Cells, Cultured
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - S0006-4971(20)78913-5 [pii]
PST - ppublish
SO  - Blood. 1994 Jun 1;83(11):3289-97.