All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells

G. Visani, P. Tosi, E. Ottaviani, A. Zaccaria, C. Baccini, S. Manfroi, R. Pastano, C. Remiddi, A. Morelli, A. L. Molinari, R. Zanchini, S. Tura

Research output: Contribution to journalArticle

Abstract

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1α, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-α were tested with and without ATRA addition. After 5 d exposure to ATRA 10-6 M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1α (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-α was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

Original languageEnglish
Pages (from-to)301-306
Number of pages6
JournalEuropean Journal of Haematology
Volume57
Issue number4
Publication statusPublished - 1996

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Acute Promyelocytic Leukemia
Tretinoin
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-6
Granulocyte Colony-Stimulating Factor
Leukemia
Interleukin-3
Interleukin-1
Interleukin-4
Interleukin-10
Clone Cells
Remission Induction
Myeloid Cells
In Vitro Techniques
Acute Myeloid Leukemia

Keywords

  • colony stimulating factors
  • cytokines
  • interleukins
  • leukemia
  • promyelocytic
  • retinoids

ASJC Scopus subject areas

  • Hematology

Cite this

Visani, G., Tosi, P., Ottaviani, E., Zaccaria, A., Baccini, C., Manfroi, S., ... Tura, S. (1996). All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells. European Journal of Haematology, 57(4), 301-306.

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells. / Visani, G.; Tosi, P.; Ottaviani, E.; Zaccaria, A.; Baccini, C.; Manfroi, S.; Pastano, R.; Remiddi, C.; Morelli, A.; Molinari, A. L.; Zanchini, R.; Tura, S.

In: European Journal of Haematology, Vol. 57, No. 4, 1996, p. 301-306.

Research output: Contribution to journalArticle

Visani, G, Tosi, P, Ottaviani, E, Zaccaria, A, Baccini, C, Manfroi, S, Pastano, R, Remiddi, C, Morelli, A, Molinari, AL, Zanchini, R & Tura, S 1996, 'All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells', European Journal of Haematology, vol. 57, no. 4, pp. 301-306.
Visani G, Tosi P, Ottaviani E, Zaccaria A, Baccini C, Manfroi S et al. All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells. European Journal of Haematology. 1996;57(4):301-306.
Visani, G. ; Tosi, P. ; Ottaviani, E. ; Zaccaria, A. ; Baccini, C. ; Manfroi, S. ; Pastano, R. ; Remiddi, C. ; Morelli, A. ; Molinari, A. L. ; Zanchini, R. ; Tura, S. / All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells. In: European Journal of Haematology. 1996 ; Vol. 57, No. 4. pp. 301-306.
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abstract = "Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1α, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-α were tested with and without ATRA addition. After 5 d exposure to ATRA 10-6 M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1α (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-α was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.",
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AU - Baccini, C.

AU - Manfroi, S.

AU - Pastano, R.

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AU - Tura, S.

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