2020Journal of Cellular ImmunologyOpen access

Cyclosporine Broadens the Therapeutic Potential of Lenalidomide in Myeloid Malignancies

Aixia Dou, Jing Fang

Open full text 5 citations

Abstract

/calpain pro-apoptotic pathway, while upregulation of RCAN1 inhibited the CaN pro-survival pathway in MDSL cells. Notably, the pharmacological CaN inhibitor, cyclosporine, enhanced the sensitivity to lenalidomide in MDS as well as acute myeloid leukemia (AML). Surprisingly, pretreatment with lenalidomide reversed the immunosuppressive effects of cyclosporine on T lymphocytes. Our studies suggest that lenalidomide mediates degradation of IKZF1, leading to derepression of GPR68 and RCAN1 that activates the Ca2+/calpain pro- apoptotic pathway and inhibits the CaN pro-survival pathway, respectively. Our studies implicate that cyclosporine extends the therapeutic potential of lenalidomide to myeloid malignancies without compromising immune function.

About this research paper

What this paper is about

/calpain pro-apoptotic pathway, while upregulation of RCAN1 inhibited the CaN pro-survival pathway in MDSL cells. Notably, the pharmacological CaN inhibitor, cyclosporine, enhanced the sensitivity to lenalidomide in MDS as well as acute myeloid leukemia (AML). Surprisingly, pretreatment with lenalidomide reversed the immunosuppressive effects of cyclosporine on T lymphocytes. Our studies suggest that lenalidomide mediates degradation of IKZF1, leading to derepression of GPR68 and RCAN1 that activates the Ca2+/calpain pro- apoptotic pathway and inhibits the CaN pro-survival pathway, respectively. Our studies implicate that cyclosporine extends the therapeutic potential of lenalidomide to myeloid malignancies without compromising immune function.

Why it matters

OpenAlex reports 5 citations for this work. Citation counts describe recorded attention and do not establish research quality.

Key contribution

A contribution statement is not available in the OpenAlex record.

Method / approach

Method details are not available in the OpenAlex metadata.

Main findings

Findings are not separately available in the OpenAlex metadata.

Limitations

Limitations are not available in the OpenAlex metadata.

Applications

Application details are not available in the OpenAlex metadata.

Available abstract

/calpain pro-apoptotic pathway, while upregulation of RCAN1 inhibited the CaN pro-survival pathway in MDSL cells. Notably, the pharmacological CaN inhibitor, cyclosporine, enhanced the sensitivity to lenalidomide in MDS as well as acute myeloid leukemia (AML). Surprisingly, pretreatment with lenalidomide reversed the immunosuppressive effects of cyclosporine on T lymphocytes. Our studies suggest that lenalidomide mediates degradation of IKZF1, leading to derepression of GPR68 and RCAN1 that activates the Ca2+/calpain pro- apoptotic pathway and inhibits the CaN pro-survival pathway, respectively. Our studies implicate that cyclosporine extends the therapeutic potential of lenalidomide to myeloid malignancies without compromising immune function.

Key concepts: Lenalidomide, Thalidomide, Pomalidomide, Myelodysplastic syndromes, Multiple myeloma, Medicine, Cereblon, Pharmacology

Related papers

Back to paper searchBrowse research topicsOriginal source
Cyclosporine Broadens the Therapeutic Potential of Lenalidomide in Myeloid Malignancies — Research Paper | ScholarLens