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Corre J.,Intergroupe Francophone du Myelome | Corre J.,French Institute of Health and Medical Research | Corre J.,University Hospital Purpan | Hebraud B.,Intergroupe Francophone du Myelome | And 2 more authors.
Stem Cells Translational Medicine | Year: 2013

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor β family discovered in a broad range of cells, as indicated by the diversity of its nomenclature. However, the only tissue that expresses a high amount of GDF15 in the physiologic state is placenta. GDF15 is easily detected in blood, and its concentration varies with age. In fact, increased blood concentration of GDF15 is associated with numerous pathological conditions. However, the biological significance underlying these observations is far from clear. GDF15 could have a positive or negative role depending on the state of cells or their environment. Furthermore, study of its biology is hampered by lack of knowledge of its receptor and thus the signaling pathways that drive its action. GDF15 seems to be an integrative signal in pathologic conditions, giving information on severity of disease. Its effectiveness in classifying patients to modulate treatment remains to be shown. Development of therapeutic interventions with GDF15 or anti-GDF15 agents remains difficult until we uncover the mechanism that drives its activity. © AlphaMed Press 2013.


Richardson P.G.,Dana-Farber Cancer Institute | Delforge M.,University Hospital Leuven | Beksac M.,Ankara University | Wen P.,Dana-Farber Cancer Institute | And 33 more authors.
Leukemia | Year: 2012

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions. © 2012 Macmillan Publishers Limited All rights reserved.

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