Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-3-6
pubmed:abstractText
All-trans retinoic acid (ATRA) has been demonstrated to be an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (APL or AML3). Complete remission is obtained by inducing granulocytic differentiation of the leukemic cells. To date, the exact mechanism through which ATRA exerts its differentiating effect is not known. The present investigation was initiated to characterize ATRA intracellular concentrations achieved in human myeloid leukemic cells in relation to their different sensitivity to ATRA differentiating effect. During the first 24 h of incubation, a significant decrease of ATRA in the culture medium and a marked increase in the intracellular concentrations were observed. Maximal uptake by the leukemic cells was reached within minutes, with levels between 20 and 260 pmol/10(6) cells (median = 100). Interestingly, a correlation between ATRA-induced differentiation and the intracellular ATRA concentration achieved was observed. In fact, patients with intracellular levels below 60 pmol/10(6) cells defined slow uptakers, never exceeded 40% differentiated cells at day 3. On the other hand, cells with 2-4-fold higher concentration (100-250 pmol/10(6) cells) achieved 100% differentiated cells at day 3. This report suggests that intracellular ATRA concentration is a key pharmacological parameter that should be taken into account to gain further insights into ATRA sensitivity in APL patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
139-45
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Differential uptake of all-trans retinoic acid by acute promyelocytic leukemic cells: evidence for its role in retinoic acid efficacy.
pubmed:affiliation
Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint-Louis, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't