Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo.

Fucoidan is one of the major sulfated polysaccharides isolated from brown seaweeds. In this study, we determined the anti-cancer activity of fucoidan on diffuse large B cell lymphoma (DLBCL) cells both in vitro and in vivo. Fucoidan inhibited the growth of DLBCL cells in a dose- and time-dependent manner, and fucoidan treatment provoked G0/G1 cell cycle arrest, which was accompanied by p21 up-regulation and cyclin D1, Cdk4, and Cdk6 down-regulation. Fucoidan also induced caspase-dependent cell apoptosis in DLBCL cell lines and primary DLBCL cell. In addition, fucoidan treatment caused the loss of mitochondrial membrane potential and the release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Fucoidan also potentiated the activities of carfilzomib in killing DLBCL cells. Oral administration of fucoidan effectively inhibited tumor growth in xenograft mouse models. Our findings reveal the novel function of fucoidan as an anti-DLBCL agent, which can be used in the clinical treatment of DLBCL.

Myeloma cells resistance to NK cell lysis mainly involves an HLA class I-dependent mechanism.

The anti-multiple myeloma (MM) potential of natural killer (NK) cells has been of rising interest in recent years. However, the molecular mechanism of NK cell cytotoxicity to myeloma cells remains unclear. In the present study, we investigated the expressions of human leukocyte antigen (HLA) class I and HLA-G in patient myeloma cells, and determined their relevance in patient tumor-cell susceptibility to NK cell cytotoxicity. Our results showed that patient myeloma cells (n = 12) were relatively resistant to NK-92 cell lysis, compared with myeloma cell lines (n = 7, P < 0.01). Gene expression profiling and flow cytometry analysis showed that both mRNA and protein of HLA class I were highly expressed in 12 patient myeloma cells. Interestingly, no or low HLA-G surface expression was detected, although multiple HLA-G transcripts were detected in these myeloma cells. NK cell function assay showed that down-regulating HLA class I expression on patient cells by acid treatment significantly increased the susceptibility of MM cells to NK-mediated lysis. Furthermore, we found that the blocking of membrane-bound HLA class I rather than HLA-G using antibodies on myeloma samples markedly increased their susceptibility to NK-mediated killing. These results demonstrated that the resistance of patient MM cells to NK lysis mainly involves an HLA class I-dependent mechanism, suggesting that HLA class I may be involved in protecting MM cells from NK-mediated attack and contribute to their immune escape in vivo.

Overexpression of IGF-IR in malignant clonal cells in bone marrow of myelodysplastic syndromes.

OBJECTIVE: To explore the expression level of insulin-like growth factor-1 receptor (IGF-IR) in malignant clone cells of myelodysplastic syndromes (MDS). METHOD: Fluorescence in situ hybridization (FISH) and immunochemistry (alkaline phosphatase antialkaline phosphatase) were used together to detect the expression of IGF-IR in the bone marrow cells of 26 MDS patients with known abnormal karyotypes. RESULT: The average IGF-IR expression level on the surface of clone cells from the 26 MDS cases was markedly elevated compared with the corresponding level in normal cells (78.2 ± 13.7% vs. 14.1 ± 14.0%, p < .0001). The percentages of malignant clone cells in all 26 MDS cases were significantly correlated with the respective percentages of IGF-IR-positive nucleated cells (r = 0.909; p < .0001). No significant difference in the IGF-IR expression level on the clone cells were observed either between high- and low-risk MDS patients or among MDS patients with different abnormal karyotypes. CONCLUSION: IGF-IR might be taken as a marker of clone cells in MDS.

An ider(17)(q10)t(15;17) with spliced long-type PML-RARA fusion transcripts in a case of acute promyelocytic leukemia.

The ider(17)(q10)t(15;17) is a relatively rare chromosomal rearrangement in acute promyelocytic leukemia patients. We describe herein a case of APL with a poor prognosis and ider(17)(q10)t(15;17)(q22;q12), which was confirmed by fluorescence in situ hybridization. Reverse transcription polymerase chain reaction (RT-PCR) and sequencing of PCR products were used to detect the PML-RARA fusion gene and delineate the sequence of the fusion transcripts. We found that the PML-RARA fusion gene of this patient was the long isoform, which only generated transcripts of a splice variant lacking PML exon 5 and a splice variant lacking PML exons 5 and 6. Although the clinical and prognostic significance of patients with an ider(17)(q10)t(15;17) remains unclear, a combination of cytogenetics and molecular biology analysis should be performed to obtain further information about this chromosomal abnormality.

[Relationship between mitochondrial DNA and myelodysplastic syndromes - review].

Mitochondria is the main place of biological oxidation and energy transform. Mitochondrial DNA encodes the complex of respiratory chain in mitochondria and its mutation can cause a series of human disease. Mitochondrial DNA mutation which observed in myelodysplastic syndrome (MDS) patients cause the MDS by the mechanism of iron metabolism disorder, gene instability and hemopoietic progenitor cell apoptosis. In this review the characteristics of mitochondrial DNA structure, the mitochondrial DNA mutation and the possible mechanism of mitochondrial DNA mutation in pathogenesis of MDS were summarized.