CD40L induces proliferation, self-renewal, rescue from apoptosis, and production of cytokines by CD40-expressing AML blasts

Donatella Aldinucci, Dalisa Poletto, Paola Nanni, Massimo Degan, Maurizio Rupolo, Antonio Pinto, Valter Gattei

Research output: Contribution to journalArticlepeer-review


Objective. Conflicting experimental and clinical results have been reported regarding the role of CD40 in acute myeloid leukemia (AML). In the present study, we analyzed the capability of CD40L/CD154 to modulate several functional aspects of CD40-expressing AML blasts. Methods. After defining the constitutive expression levels of CD40 in a wide panel (n = 67) of AMLs and evaluating the capability of cytokines to modulate its expression, we investigated the effects of CD40 engagement by soluble (s) CD40L on proliferation, self-renewal capacity, apoptosis, homotypic adhesion, and cytokine production of leukemia cells. Results. CD40 was detected in blast cells from about 37% of AMLs, the highest frequency being documented in monocytic subtypes, and its expression was upregulated or de novo induced by treatment with interleukin (IL)-1α, IL-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ, and tumor necrosis factor-α. Exposure of CD40+ AML blasts to sCD40L resulted in a dose-dependent proliferative response, enhancement of clonogenic growth and self-renewal capacity, and a striking increase in colony size. CD40 engagement was able to rescue AML blasts from apoptosis induced by serum deprivation, as demonstrated by reduced expression of APO2.7 and annexin-V binding, as well as upregulation of the anti-apoptotic protein bcl-xL. CD40 triggering upregulated cell surface expression of the adhesion molecules CD54, CD58, and CD15 and resulted in homotypic aggregation of leukemia cells at least in part CD54-dependent. An increased production of IL-6 and GM-CSF by CD40+ AML blasts was also documented upon sCD40L exposure. Conclusions. This study indicates a possible involvement of CD40 in the interactions of AML blasts with other growth-sustaining microenvironmental accessory cells and immune effectors, in turn expressing CD40L. Caution in the use of CD40 triggering in immunotherapy of AMLs is also suggested.

Original languageEnglish
Pages (from-to)1283-1292
Number of pages10
JournalExperimental Hematology
Issue number11
Publication statusPublished - Nov 1 2002

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation


Dive into the research topics of 'CD40L induces proliferation, self-renewal, rescue from apoptosis, and production of cytokines by CD40-expressing AML blasts'. Together they form a unique fingerprint.

Cite this