Generation of immunologically active dendritic cells from chronic myelomonocytic leukemia (CMML)

David Claxton, Despee Konneh, Richard Champlin, Aniruddha Choudhury

Research output: Contribution to journalArticle

Abstract

We have previously shown that dendritic cells (DC) may be generated from leukemic cells of chronic myelogenous leukemia and acute myelogenous leukemia patients and that these DC may be used to stimulate autologous anti-leukemic cytotoxic cells. DC have been generated with the cytokines GM-CSF, IL-4, and TNFa. To expand the range of this observation, we studied a variety of conditions for the culture of immunoreactive DC from patients with CMML. Eight patients were studied. Peripheral blood mononuclear cells were cultured for periods of six to fourteen days. As measured by increase in CD-86 and CD-80 expression and loss of expression of CD-14, the cytokine combination GMCSF, IL-4, TNFa effectively drove DC differentiation in seven of the eight cases. In six of these seven cases this differentiation was extremely vigorous, with the bulk of the final cells showing CD-80 or CD-86 expression. In three patients adherent cells showed the greatest DC differentiation potential. The limited availability of clinical grade IL-4 and TNFa is a major impediment to the treatment of patients with myeloid disorders with these cell preparations. Recent data has suggested that IFNa together with GM-CSF may generate DC from normal monocytes. Accordingly in three patients the combination of GM-CSF. IL-4, and TNFa was compared to GM-CSF with IFNa with or without TNFa. In all cases GM-CSF, IL-4, and TNFa were superior to the cytokine combinations in which IFNa was substituted for IL-4. CD-80 and CD-86 expression was dramatically increased in the IL-4 containing cytokine combinations and IL-4 suppressed CD-14 expression (unlike IFNa). GM-CSF, IL-4, and TNFa generated DC which consistently stimulated alloMLR four to ten fold better than did fresh leukemic cells from the same patients. In two patients the GM-CSF, IL-4, and TNFa combination was significantly superior to either GM-CSF and IFNa, or GM-CSF, IFNa, and TNFa. Thus, our data suggests that for chronic myelomonocytic leukemia the cytokine combination of GMCSF. IL-4, and TNFa is superior to cytokine combinations in which IFNa has been substituted for IL-4. In patients with this diagnosis, IL-4 would appear to be important for the execution of clinical trials.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

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Leukemia, Myelomonocytic, Chronic
Interleukin-4
Dendritic Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
Cell Differentiation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Acute Myeloid Leukemia

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Claxton, David ; Konneh, Despee ; Champlin, Richard ; Choudhury, Aniruddha. / Generation of immunologically active dendritic cells from chronic myelomonocytic leukemia (CMML). In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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Claxton, D, Konneh, D, Champlin, R & Choudhury, A 2000, 'Generation of immunologically active dendritic cells from chronic myelomonocytic leukemia (CMML)', Blood, vol. 96, no. 11 PART II.

Generation of immunologically active dendritic cells from chronic myelomonocytic leukemia (CMML). / Claxton, David; Konneh, Despee; Champlin, Richard; Choudhury, Aniruddha.

In: Blood, Vol. 96, No. 11 PART II, 01.12.2000.

Research output: Contribution to journalArticle

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T1 - Generation of immunologically active dendritic cells from chronic myelomonocytic leukemia (CMML)

AU - Claxton, David

AU - Konneh, Despee

AU - Champlin, Richard

AU - Choudhury, Aniruddha

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AB - We have previously shown that dendritic cells (DC) may be generated from leukemic cells of chronic myelogenous leukemia and acute myelogenous leukemia patients and that these DC may be used to stimulate autologous anti-leukemic cytotoxic cells. DC have been generated with the cytokines GM-CSF, IL-4, and TNFa. To expand the range of this observation, we studied a variety of conditions for the culture of immunoreactive DC from patients with CMML. Eight patients were studied. Peripheral blood mononuclear cells were cultured for periods of six to fourteen days. As measured by increase in CD-86 and CD-80 expression and loss of expression of CD-14, the cytokine combination GMCSF, IL-4, TNFa effectively drove DC differentiation in seven of the eight cases. In six of these seven cases this differentiation was extremely vigorous, with the bulk of the final cells showing CD-80 or CD-86 expression. In three patients adherent cells showed the greatest DC differentiation potential. The limited availability of clinical grade IL-4 and TNFa is a major impediment to the treatment of patients with myeloid disorders with these cell preparations. Recent data has suggested that IFNa together with GM-CSF may generate DC from normal monocytes. Accordingly in three patients the combination of GM-CSF. IL-4, and TNFa was compared to GM-CSF with IFNa with or without TNFa. In all cases GM-CSF, IL-4, and TNFa were superior to the cytokine combinations in which IFNa was substituted for IL-4. CD-80 and CD-86 expression was dramatically increased in the IL-4 containing cytokine combinations and IL-4 suppressed CD-14 expression (unlike IFNa). GM-CSF, IL-4, and TNFa generated DC which consistently stimulated alloMLR four to ten fold better than did fresh leukemic cells from the same patients. In two patients the GM-CSF, IL-4, and TNFa combination was significantly superior to either GM-CSF and IFNa, or GM-CSF, IFNa, and TNFa. Thus, our data suggests that for chronic myelomonocytic leukemia the cytokine combination of GMCSF. IL-4, and TNFa is superior to cytokine combinations in which IFNa has been substituted for IL-4. In patients with this diagnosis, IL-4 would appear to be important for the execution of clinical trials.

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