Promyelocytic leukemia-specific PML-retinoic acid α receptor fusion protein interferes with erythroid differentiation of human erythroleukemia K562 cells

• Published in: Cancer research (Chicago, Ill.) Vol. 55; no. 2; pp. 440 - 443
• Main Authors: GRIGNANI, F, TESTA, U, FAGIOLI, M, BARBERI, T, MASCIULLI, R, MARIANI, G, PESCHLE, C, PELICCI, P. G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.1995
• Subjects: Biological and medical sciences; Cell Differentiation - drug effects; Cell Division - drug effects; Fetal Hemoglobin - metabolism; Glycophorin - metabolism; Hematologic and hematopoietic diseases; Humans; Leukemia, Erythroblastic, Acute - metabolism; Leukemia, Erythroblastic, Acute - pathology; Leukemia, Promyelocytic, Acute - genetics; Leukemia, Promyelocytic, Acute - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Neoplasm Proteins; Nuclear Proteins; Promyelocytic Leukemia Protein; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Recombinant Fusion Proteins - metabolism; Retinoic Acid Receptor alpha; Transcription Factors - genetics; Transcription Factors - metabolism; Tretinoin - pharmacology; Tumor Cells, Cultured; Tumor Suppressor Proteins; Chromosomal aberration; Erythroleukemia; Human; Promyelocytic leukemia; Erythroid cell; Pathogenesis; Acute; Malignant hemopathy; Cell differentiation; In vitro; Myeloproliferative syndrome; Established cell line; Abnormal chromosome; Retinoic acid; Tumor cell; Biological receptor; Chromosome translocation
• ISSN: 0008-5472; 1538-7445

Acute promyelocytic leukemia (APL) is characterized by a t(15;17) chromosomal translocation with breakpoints within the retinoic acid alpha receptor (RAR alpha) gene on 17 and the PML gene, which encodes a putative transcription factor, on 15. A PML-RAR alpha fusion protein is formed as a consequence of the translocation. We show here that expression of the PML-RAR alpha protein in K562 erythroleukemia cells results in a reduced expression of erythroid differentiation markers and a reduced sensitivity to the erythroid differentiative action of heme. Overexpression of RAR alpha, but not of PML, elicited a similar inhibition of K562 erythroid differentiation. These findings indicate that overexpression of either RAR alpha or PML/RAR alpha interferes with erythroid differentiation and support the hypothesis that RAR alpha is involved in the regulation of normal hematopoiesis and alteration of the RAR alpha signaling by PML/RAR alpha is implicated in the promyelocytic leukemogenesis.