Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma

G. Visani, R. M. Lemoli, P. Tosi, F. Verlicchi, B. Gamberi, A. R. Cenacchi, R. Colombini, M. Fogli, D. Russo, E. Zuffa, R. Fanin, S. Tura

Research output: Contribution to journalArticle

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Abstract

PTT-119, a new synthetic alkylating compound, has shown a marked "in vitro" inhibitory effect on chronic myeloid leukemia (CML) granulo-monocytic precursors (CFU-GM) at doses greater than 5 μg/ml. Based on previous experiences of synergistic associations between alkylating drugs and biological modifiers, we tested the effects of low doses of PTT-119 (from 0.1 to 1 μg/ml) in concert with alpha, gamma, or alpha + gamma interferons and compared to IFNs alone, in order to investigate an alternative choice for treatment of CML patients in chronic phase. Our results showed a significantly higher CFU-GM cloning inhibition after addition of 100 or 1,000 U/ml of alpha IFN to 0.1 μg/ml PTT-119 (from 39.6% ± 26.6 SD to 80.7% ± 10 SD and 91.5% ± 8 SD, respectively), while gamma IFN resulted in only a slight increase in colony growth inhibition when compared to the drug used alone. The association of alpha plus gamma IFN coupled with PTT-119 treatment did not significantly improve the results observed after exposure of leukemic progenitors to PTT-119 and alpha IFN alone. We conclude that a combined treatment with PTT-119 and IFN is probably worth testing both for purging methods before autologous bone marrow transplantation and for in vivo administration in chronic myeloid leukemia.

Original languageEnglish
Pages (from-to)287-290
Number of pages4
JournalBlut
Volume60
Issue number5
DOIs
Publication statusPublished - May 1990

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon-alpha
Granulocyte-Macrophage Progenitor Cells
Autologous Transplantation
Bone Marrow Transplantation
Pharmaceutical Preparations
Interferon-gamma
ambamustine
human IFNG protein
Organism Cloning
Therapeutics
Growth

Keywords

  • Alpha interferon
  • Autologous bone marrow transplantation
  • Chronic myeloid leukemia
  • Gamma interferon
  • PTT-119

ASJC Scopus subject areas

  • Hematology

Cite this

Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma. / Visani, G.; Lemoli, R. M.; Tosi, P.; Verlicchi, F.; Gamberi, B.; Cenacchi, A. R.; Colombini, R.; Fogli, M.; Russo, D.; Zuffa, E.; Fanin, R.; Tura, S.

In: Blut, Vol. 60, No. 5, 05.1990, p. 287-290.

Research output: Contribution to journalArticle

Visani, G. ; Lemoli, R. M. ; Tosi, P. ; Verlicchi, F. ; Gamberi, B. ; Cenacchi, A. R. ; Colombini, R. ; Fogli, M. ; Russo, D. ; Zuffa, E. ; Fanin, R. ; Tura, S. / Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma. In: Blut. 1990 ; Vol. 60, No. 5. pp. 287-290.
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abstract = "PTT-119, a new synthetic alkylating compound, has shown a marked {"}in vitro{"} inhibitory effect on chronic myeloid leukemia (CML) granulo-monocytic precursors (CFU-GM) at doses greater than 5 μg/ml. Based on previous experiences of synergistic associations between alkylating drugs and biological modifiers, we tested the effects of low doses of PTT-119 (from 0.1 to 1 μg/ml) in concert with alpha, gamma, or alpha + gamma interferons and compared to IFNs alone, in order to investigate an alternative choice for treatment of CML patients in chronic phase. Our results showed a significantly higher CFU-GM cloning inhibition after addition of 100 or 1,000 U/ml of alpha IFN to 0.1 μg/ml PTT-119 (from 39.6{\%} ± 26.6 SD to 80.7{\%} ± 10 SD and 91.5{\%} ± 8 SD, respectively), while gamma IFN resulted in only a slight increase in colony growth inhibition when compared to the drug used alone. The association of alpha plus gamma IFN coupled with PTT-119 treatment did not significantly improve the results observed after exposure of leukemic progenitors to PTT-119 and alpha IFN alone. We conclude that a combined treatment with PTT-119 and IFN is probably worth testing both for purging methods before autologous bone marrow transplantation and for in vivo administration in chronic myeloid leukemia.",
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AU - Gamberi, B.

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