Tumor necrosis factor α down-regulates c-myc mRNA expression and induces in vitro monocytic differentiation in fresh blast cells from patients with acute myeloblastic leukemia

Gaetano Bergamaschi, Carmelo Carlo-Stella, Mario Cazzola, Pasqualina De Fazio, Paolo Pedrazzoli, Fiorenzo A. Peverali, Giuliano Della Valle

Research output: Contribution to journalArticle

Abstract

We have studied tumor necrosis factor α (TNF-α) for its capacity to induce differentiation and to modulate c-myc and c-fms protooncogene mRNA expression in fresh blasts from 10 patients with acute myeloblastic leukemia (AML). Bone marrow blast cells were grown in suspension cultures in the presence of 500 U/ml (62 ng/ml) of TNF-α for 7 days. Induction of differentiation was assessed by means of morphology, cytochemistry, immunophenotyping (CD11b, CD13, CD14, CD33), and nitroblue tetrazollum reduction. In all cases, exposure of leukemic blasts to TNF-α resulted in phenotypic changes consistent with induction of differentiation, although a marked variability in degree and type of response was observed. The majority of cases developed monocytic morphology and showed significant increases (χ2 test, p <0.05) in phagocytic activity and/or expression of ANAE and myelomonocytic differentiation antigens (CD11b, CD14). TNF-α reduced c-myc mRNA level over a period of 24 hr In four of six cases studied: the two cases with no down-regulation were the least responsive in terms of myelomonocytic differentiation. These results confirm those obtained with leukemic cell lines, suggesting that TNF-α can induce differentiation of fresh AML blasts, mainly toward the monocytic lineage, and that induction of differentiation seems to be closely linked to down-regulation of c-myc mRNA expression over the first 24 hr rather than to attenuation of cellular proliferation per se.

Original languageEnglish
Pages (from-to)426-430
Number of pages5
JournalLeukemia
Volume4
Issue number6
Publication statusPublished - Jun 1990

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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