title: The expression of cellular retinoid binding proteins in non-APL leukemic cells and its association with retinoid sensitivity.
abstract: Retinoic acid (RA) has important effects on cell differentiation and cell growth and on normal embryonic development. Intracellular retinoid signaling induced by endogenous or exogenous RA is regulated by retinoid binding proteins such as CRBPI, CRABPI and CRABPII and there are data suggesting that the expression of these proteins can influence the sensitivity to the growth inhibitory effects of ATRA. In this study, we investigated the basal and ATRA-induced expression of CRBPI and CRABPI and II in leukemic cell lines and in cells from patients with acute myeloid leukemia (AML). CRBPI as well as CRABPI and II were expressed in all tested cell lines and in leukemic cells from all 18 AML-patients. CRABPII mRNA expression was more abundant than CRBPI and CRABPI in both the cell lines and the patient cells but the levels compared the house keeping gene was lower in the patient cells. In all cell lines and in 69% of the patient samples, ATRA did upregulate CRABPII whereas CRBPI exhibited a varying response and CRABPI was more commonly downregulated. The sensitivity to the growth inhibitory effects of ATRA did not correlate with the basal expression of any of these proteins. However, ATRA-induced upregulation of CRABPII did significantly correlate with the ATRA sensitivity (p < 0.005) as well as with ATRA-induced upregulation of the retinoid receptor RARbeta (p < 0.05). We conclude that the retinoid binding proteins CRBPI and CRABPI and II are expressed in myeloid leukemic cells of non-M3 type but that the level of expression does not affect ATRA sensitivity.
authors.affiliation: Department of Hematology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. soren.lehmann@medhs.ki.se
authors.forename: S
authors.initials: S
authors.lastname: Lehmann
authors.forename: C
authors.initials: C
authors.lastname: Paul
authors.forename: H
authors.initials: H
authors.lastname: Törmä
mesh_terms: D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics*; D012177:Retinol-Binding Proteins / Q000032:analysis / Q000235:genetics*; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C518456:RBP1 protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; C082925:retinoic acid receptor beta; D014212:Tretinoin