PMA-treated K-562 leukemia cells mediate a TH2-specific expansion of CD4+ T cells in vitro

Baker, Erich J.; Ichiki, Albert T.; Hodge, James W.; Sugantharaj, D. G.; Bamberger, Elena G.; Lozzio, Carmen B.

doi:10.1016/s0145-2126(00)00082-5

Cited by 5 publications

(1 citation statement)

References 36 publications

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“…Although the expression of CD41 has not been determined for DC, it is a receptor for the extracellular matrix and may play a role in the adhesion of myeloid cells (including DC) during cellular migration. Furthermore, Baker et al (72) demonstrated that CD61 ϩ PMA-treated K562 (stimulated with a lower PMA dose than that used in our studies) can mediate CD4 ϩ T cell expansion in vitro, a property they ascribed to accessory cell function of differentiated K562. We suggest that this ability to activate T cells is due to PMA-induced differentiation of K562 into cells with DC characteristics, consistent with the aggregate of findings demonstrating that CD34 ϩ HPC and primary CML blasts can undergo DC differentiation in response to either direct PKC activation or exogenous cytokines.…”

Section: Discussionmentioning

confidence: 47%

Induced Dendritic Cell Differentiation of Chronic Myeloid Leukemia Blasts Is Associated with Down-Regulation of BCR-ABL

Lindner

Kharfan‐Dabaja

Ayala

et al. 2003

The Journal of Immunology

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Although differentiation of leukemic blasts to dendritic cells (DC) has promise in vaccine strategies, the mechanisms underlying this differentiation and the differences between leukemia and normal progenitor-derived DC are largely undescribed. In the case of chronic myeloid leukemia (CML), understanding the relationship between the induction of DC differentiation and the expression of the BCR-ABL oncogene has direct relevance to CML biology as well as the development of new therapeutic approaches. We now report that direct activation of protein kinase C (PKC) by the phorbol ester PMA in the BCR-ABL+ CML cell line K562 and primary CML blasts induced nonterminal differentiation into cells with typical DC morphology (cytoplasmic dendrites), characteristic surface markers (MHC class I, MHC class II, CD86, CD40), chemokine and transcription factor expression, and ability to stimulate T cell proliferation (equivalent to normal monocyte-derived DC). PKC-induced differentiation was associated with down-regulation of BCR-ABL mRNA expression, protein levels, and kinase activity. This down-regulation appeared to be signaled through the mitogen-activated protein kinase pathway. Therefore, PKC-driven differentiation of CML blasts into DC-like cells suggests a potentially novel strategy to down-regulate BCR-ABL activity, yet raises the possibility that CML-derived DC vaccines will be less effective in presenting leukemia-specific Ags.

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Section: Discussionmentioning

confidence: 47%