In vitro apoptotic response of freshly isolated chronic myeloid leukemia cells to all-trans retinoic acid and cytosine arabinoside

• Published in: Acta haematologica Vol. 104; no. 2-3; p. 57
• Main Authors: Stagno, F, Guglielmo, P, Consoli, U, Inghilterra, G, Giustolisi, G M, Palumbo, G A, Giustolisi, R
• Format: Journal Article
• Language: English
• Published: Switzerland 01.01.2000
• Subjects: Antigens, CD - biosynthesis; Antigens, Differentiation, Myelomonocytic - biosynthesis; Antimetabolites, Antineoplastic - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis - drug effects; Biomarkers, Tumor - blood; Biomarkers, Tumor - immunology; Cell Differentiation - drug effects; Cell Separation; Cytarabine - pharmacology; DNA Fragmentation - drug effects; Electrophoresis, Agar Gel; Female; Granulocytes - drug effects; Granulocytes - pathology; Humans; Immunophenotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemia, Myeloid, Chronic-Phase - blood; Leukemia, Myeloid, Chronic-Phase - immunology; Leukemia, Myeloid, Chronic-Phase - pathology; Macrophage-1 Antigen - biosynthesis; Male; Middle Aged; Sialic Acid Binding Ig-like Lectin 3; Tretinoin - pharmacology; Tumor Cells, Cultured
• ISSN: 0001-5792
• DOI: 10.1159/000039753

Chronic myeloid leukemia (CML) is a hematological malignancy resulting from clonal expansion and massive accumulation of leukemic myeloid cells that retain differentiation and maturation capacity. Since CML cell accumulation has been related to apoptosis inhibition by the product of the BCR-ABL gene, attempts to eradicate leukemic cells would require therapeutic drugs able to overcome this inherent resistance. Here, we investigated in vitro the apoptotic effect of all-trans retinoic acid (ATRA) and cytosine arabinoside (ARA-C), employed alone, in combination or in sequence, on freshly isolated cells from 10 patients with chronic-phase CML. Our cell cultures showed that both ATRA and ARA-C were able to induce apoptosis in CML cells, even if ARA-C resulted more effective than ATRA. The combined use of ATRA and ARA-C seemed to have only an additive effect while the sequential use did not show any advantage. These in vitro observations indicate that ATRA and ARA-C may be effective in reducing CML cells through apoptosis induction, suggesting that it could be worthwhile to examine ATRA and ARA-C combinations in the therapy of CML.