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What's New In Research - September 21, 2003
Genetic analysis is yielding more information on the complicated formation and progress of multiple myeloma.
© Copyright 2003 Immunotherapy Weekly via NewsRx.com

According to recent research from the United States, "Multiple myeloma (MM) is a rare but uniformly fatal malignancy of antibody-secreting plasma cells (PCs). Although several key molecular events in disease initiation or progression have been confirmed (e.g. FGFR3 /MMSET activation) or implicated (e.g. chromosome 13 deletion), the mechanisms of MM development remain enigmatic. Importantly, although generally being indistinguishable morphologically, MM exhibits a tremendous degree of variability in clinical course, with some patients surviving only months and others many years.

"However, current laboratory parameters can account for <20% of this outcome variability. Furthermore, the means by which current drugs impart their anti-MM effect are also mostly unknown. In addition, the mechanisms by which MM cells contribute to serious comorbidities, such as osteopenia and/or focal lytic lesions of bone, are also poorly understood. Finally, very little knowledge exists concerning the molecular events leading to benign hyperplasia and/or overt malignancy of PCs," wrote J.D. Shaughnessy and colleagues from the University of Arkansas.

The researchers concluded: "Given that abnormal gene expression lies at the heart of most, if not all, cancers, high-throughput global gene expression profiling has become a powerful tool for investigating molecular biology and clinical behavior of diseases. Here, we discuss recent progress made in addressing many of the above issues through the molecular dissection of the transcriptome of normal PCs and MM."

Shaughnessy and colleagues published their study in Immunological Reviews (Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling. Immunol Rev, 2003;194(1):140-163).

For additional information, contact J.D. Shaughnessy, University Arkansas Med Science, Donna D & Donald M Lambert Laboratory Myeloma Genetics, Myeloma Institute Research & Therapy, 4301 W Markham St., Mail Slot 706, Little Rock, AR 72205, USA.

Rheumatoid Synovium; X-box binding protein-1 is involved in plasma cell differentiation
© Copyright 2003 Immunotherapy Weekly via NewsRx.com

According to a study from the United States, "X-box binding protein-1 (XBP-1) is a transcription factor essential for plasma cell differentiation. XBP-1 transcripts are found at high levels in plasma cells from rheumatoid synovium and myeloma cell lines. Lymphoid chimeras deficient in XBP-1 have a profound defect in plasma cell differentiation, with few plasma cells in their periphery and severely reduced serum immunoglobulin levels.

"When introduced into B-lineage cells, XBP-1 initiates plasma cell differentiation. XBP-1 is also the mammalian homologue of the yeast transcription factor Hac1p, an important component of the unfolded protein response (UPR). The UPR allows cells to tolerate conditions of endoplasmic reticulum (ER) stress caused by misfolded proteins. Studies examining the relationship between plasma cell differentiation, XBP-1, and the UPR demonstrate that this novel signaling system is vital for plasma cell differentiation," wrote N.N. Iwakoshi and coauthors.

The researchers concluded: "Signals that induce plasma cell differentiation and the UPR cooperate via XBP-1 to induce terminal B-cell differentiation. Additionally, XBP-1 plays an important role in the regulation of interleukin-6 production, a cytokine essential for plasma cell survival."

Iwakoshi and colleagues published the results of their research in Immunological Reviews (The X-box binding protein-1 transcription factor is required for plasma cell differentiation and the unfolded protein response. Immunol Rev, 2003;194(1):29-38).

For additional information, contact L.H. Glimcher, Harvard University, School Publ Hlth, Dept Immunology & Infection Diseases, 651 Huntington Avenue, FXB-2, Boston, MA 02115, USA.

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