Induction of retinoic acid-binding protein in normal and malignant human myeloid cells by retinoic acid in acute promyelocytic leukemia patients.
Retinoic acid has striking effects on development and cell differentiation. Its biological effect is a highly regulated process that is controlled by specific proteins. In the nucleus, different retinoic acid receptors have been identified and their genes cloned. In the cytosol, retinoid binding proteins, cellular retinoic acid-binding protein and cellular retinol-binding protein, have been correlated with normal and malignant tissue differentiation. Recently, differentiation therapy of acute promyelocytic leukemias (AML3 subtype) with all-trans-retinoic acid has been shown to be an efficient alternative to chemotherapy. The retinoic acid receptor alpha gene has been shown to be specifically rearranged in AML3 through the t(15;17) translocation. The molecular basis of the effect to reverse the leukemic phenotype of all-trans-retinoic acid is not yet elucidated. To further study retinoic acid efficacy in AML3 leukemia, retinoic acid-binding proteins were studied in the cytosol extracts of hematopoietic cells. No retinoic acid binding activity was detected in normal or malignant hematopoietic cells whether sensitive or not to retinoic acid. However, detectable binding to a cytosolic protein corresponding to cellular retinoic acid-binding protein (M(r) 15,000, Kd 3 nM) was observed in the bone marrow cells of AML3 patients undergoing all-trans-retinoic acid therapy. We suggest that both the induction and subsequent presence of cellular retinoic acid-binding protein may influence the therapeutic efficacy of retinoic acid and must be taken into account when studying its effect in acute promyelocytic patients.
Cornic
M
M
Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint-Louis, Paris, France.
Delva
L
L
Guidez
F
F
Balitrand
N
N
Degos
L
L
Chomienne
C
C
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000628:therapy; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D014212:Tretinoin