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

F Grignani; U Testa; M Fagioli; T Barberi; R Masciulli; G Mariani; C Peschle; P G Pelicci

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

Cancer Res. 1995 Jan 15;55(2):440-3.

Authors

F Grignani¹, U Testa, M Fagioli, T Barberi, R Masciulli, G Mariani, C Peschle, P G Pelicci

Affiliation

¹ Istituto di Clinica Medica I, Policlinico Monteluce, Perugia, Italy.

PMID: 7529139

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / drug effects
Cell Division / drug effects
Fetal Hemoglobin / metabolism
Glycophorins / metabolism*
Humans
Leukemia, Erythroblastic, Acute / metabolism*
Leukemia, Erythroblastic, Acute / pathology*
Leukemia, Promyelocytic, Acute / genetics
Leukemia, Promyelocytic, Acute / metabolism*
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

Substances

Glycophorins
Neoplasm Proteins
Nuclear Proteins
Promyelocytic Leukemia Protein
RARA protein, human
Receptors, Retinoic Acid
Recombinant Fusion Proteins
Retinoic Acid Receptor alpha
Transcription Factors
Tumor Suppressor Proteins
PML protein, human
Tretinoin
Fetal Hemoglobin