The role that hepatocyte growth factor plays in multiple myeloma is unclear.
Copyright 2003 Hematology Week via NewsRx.com
According to published research from Greece, "hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity."
"Forty-seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie-Salmon classification). Bone lesions were scored from 0 to 3, according to X-ray findings. Serum osteocalcin (OC), interleukin-6 (IL-6), TNF-alpha, beta(2)-microglobulin (beta(2)M), CRIP, calcium, and 24-hr urine N-telopeptide cross-links of collagen breakdown (NTx) were determined," described M.G. Alexandrakis and colleagues, University Hospital of Heraklion, Division of Medicine.
"HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, p<0.05). Similarly, NTx, IL-6, TNF-alpha, CRIP, beta(2)M, and calcium increased significantly with advancing stage (p<0.01)," researchers wrote.
"OC was higher at stage I in comparison to stages II and III (p<0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL-6 and TNF-alpha and less with beta(2)M, CRP, NTx, and OC."
"We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL-6 and TNF-alpha, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified," concluded Alexandrakis and coworkers.
Alexandrakis and colleagues published their findings in American Journal of Hematology (Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: Correlation with markers of disease activity. Am J Hematol, 2003;72(4):229-233).
Additional information can be obtained by contacting M.G. Alexandrakis, University Hospital of Heraklion, Division of Medicine, POB 13522, Iraklion, Crete, Greece.
Methylation of SOCS-1 silences the negative regulation of cytokines and is frequent in multiple myeloma.
Copyright 2003 Cancer Gene Therapy Week via NewsRx.com
According to recent research from the United States, "The suppressor of cytokine signaling (SOCS) family of proteins has been implicated in the negative regulation of several cytokine pathways, particularly the receptor-associated tyrosine kinase/signal transducer and activator of transcription (Jak/STAT) pathways of transcriptional activation.
"SOCS-1 (also known as JAB and SSI-1) inhibits signaling by many cytokines. Because of the previously observed hypermethylation-associated inactivation of SOCS-1 in hepatocellular carcinoma and the critical role of IL-6 as a survival factor in multiple myeloma (MM), we examined CpG island methylation of the SOCS-1 gene in MM cell lines and primary MM samples.
"Aberrant SOCS-1 methylation was found in the IL-6 dependent MM cell lines U266 and XG1, which correlated with transcriptional silencing. Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine (DAC) upregulated SOCS-1 expression.
"Methylation associated inactivation of SOCS-1 in hematopoietic cell lines correlated with greater sensitivity to the chemical JAK inhibitor AG490. Using methylation specific PCR, we found that SOCS-1 is hypermethylated in 62.9% (23/35) of MM patient samples.
"In contrast, methylation analysis of malignant lymphomas of various histologies revealed SOCS-1 hypermethylation in only 3.2% (2/62), and there was no methylation of SOCS-1 in normal peripheral blood leukocytes or bone marrow cells," wrote O. Galm and colleagues from Johns Hopkins University.
The researchers concluded, "SOCS-1 is frequently inactivated by hypermethylation in MM patients. Silencing of the SOCS-1 gene may impair negative regulation of the Jak/STAT pathway and therefore result in greater responsiveness to cytokines, thus supporting survival and expansion of MM cells."
Galm and colleagues published their study in Blood (SOCS-1, a negative regulator of cytokine signaling, is frequently silenced by methylation in multiple myeloma. Blood, 2003;101(7):2784-2788).
For additional information, contact J.G. Herman, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans St., Room 543, Baltimore, MD 21231, USA.