Human myeloma cell apoptosis induced by interferon‐α

Abstract

Although there have been reports regarding the clinical effectiveness of IFNα in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy‐carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour‐cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFNα using five human myeloma cell lines which were established without any additional supplementation of IL‐6. In addition, the mRNA expression levels of apoptosis‐related genes employing the reverse transcriptase‐polymerase chain reaction (RT‐PCR) were also analysed with the KMS‐12‐PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFNα. Based on the results, it was determined that IFNα induced myeloma cell apoptosis in a dose‐dependent manner, but the sensitivity to IFNα in the cell lines examined varied and one cell line revealed growth stimulation by IFNα. In addition, the apoptosis induced by IFNα did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL‐6, IL‐6R, IRF1 and IRF2 genes were up‐regulated in KMS‐12‐PE cells cultured with IFNα. Therefore these genes may play an important role during apoptosis induced by IFNα.

Type I-IFNs control GVHD and GVL responses after transplantation

“…Type I-IFN has also been shown to promote apoptosis in several tumor cell lines in vitro, including multiple myeloma and acute lymphoblastic leukemia. [41][42][43] Together with the in vivo data presented here, this provides a rationale for studying the expression of the type I-IFN receptor on primary human hematopoietic malignancies. In receptor-positive malignancies, the administration of type I-IFN after BM transplantation may augment the sensitivity of residual malignancy to GVL responses and may be worthy of study in patients at very high risk or relapse (eg, myeloma, primary refractory acute myeloid leukemia).…”

Receptor synergy of interleukin-6 (IL-6) and insulin-like growth factor-I in myeloma cells that highly express IL-6 receptor α

“…For conventional PCR, 1 L cDNA was amplified using 2.5 U Taq DNA polymerase (Takara Bio, Kusatsu, Japan), and for real-time PCR to detect the gene expression quantitatively, LightCycler reagents and instruments (Roche, Mannheim, Germany) were used according to the manufacturer's instructions. The sequences of the used primers for p21 Cip1/Waf1 (Ookawa et al 44 ) and bax 45 were described elsewhere. The primers for Fas ligand gene (sense, 5Ј-CCT CCA GGC ACA GTT CTT CC-3Ј; antisense, 5Ј-TAC CAA GGC AAC CAG AAC CA-3Ј) and for p27 Kip1 gene (sense, 5Ј-GGG GCT CCG GCT AAC TCT GA-3Ј; antisense, 5Ј-GGC TTC TTG GGC GTC TGC TC-3Ј) were also used for PCR.…”

G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells

“…A review by the European Myeloma Research Network identified beneficial effects of IFNs in 3 randomized studies and no effect in 3 others (6). Depending on experimental conditions, IFNs can either stimulate or inhibit cell survival or induce apoptosis in myeloma cells (7)(8)(9)(10)(11). Induction of TRAIL (also known as Apo2L) has been proposed to mediate apoptosis induced by IFN-α in myeloma cells and in solid tumors (9,12,13).…”