Multiple Myeloma and Immunosecretory Disorders

Shaheen, Saad P.; Talwalkar, Sameer S.; Medeiros, L. Jeffrey

doi:10.1097/pap.0b013e31817cfcd6

Cited by 19 publications

(13 citation statements)

References 49 publications

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“…MM is often preceded by a common premalignant tumour, named monoclonal gammopathy of undetermined significance (MGUS). Clinical features include a monoclonal immunoglobulin peak or M component in the serum, hypercalcemia, bone fractures, fatigue, persistant infections, anaemia, and kidney failure (Sirohi et al, 2004;Shaheen et al, 2008). While normal PCs are generally arrested in the G1 phase of the cell cycle, MM cells have lost their cell cycle controls.…”

Section: Multiple Myelomamentioning

confidence: 99%

The role of the insulin-like growth factor 1 receptor axis in multiple myeloma

Valckenborgh

Camp

et al. 2009

Archives of Physiology and Biochemistry

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Multiple myeloma remains a fatal B cell malignancy with severe clinical features such as anaemia and bone fractures, caused by the predominant localization of the myeloma cells in the bone marrow (BM). The MM cells first migrate towards the BM, followed by their clonal expansion and induction of angiogenesis and osteolysis. Insulin-like growth factor 1 or IGF-1 is a cytokine which plays a role in myeloma development. Besides serving as a growth and survival factor, it attracts the cells towards the BM, and is involved in the angiogenesis process. This makes the IGF-1R an interesting target for therapeutical interventions. Apart from mediating aspects of the malignant phenotype, it also appears not to be an absolute requirement for normal cell homeostasis. Various strategies targeting the IGF-1R have emerged with the two main strategies being blocking antibodies and small molecule inhibitors. After encouraging preclinical results both strategies are now in clinical trials.

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Section: Multiple Myelomamentioning

confidence: 99%

The role of the insulin-like growth factor 1 receptor axis in multiple myeloma

Valckenborgh

Camp

et al. 2009

Archives of Physiology and Biochemistry

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“…Ig deposits are frequently associated with B cell malignancy (16). Autoantigens may be involved in the stimulation of B cell proliferative diseases, as suggested by the restricted use of particular V genes (17) and the accumulation of somatic mutations (18).…”

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confidence: 99%

Intra-Golgi Formation of IgM–Glycosaminoglycan Complexes Promotes Ig Deposition

Khan

Cox

Nishimoto

et al. 2011

The Journal of Immunology

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Immune complexes arise from interactions between secreted Ab and Ags in the surrounding milieu. However, it is not known whether intracellular Ag–Ab interactions also contribute to the formation of extracellular immune complexes. In this study, we report that certain murine B cell hybridomas accumulate intracellular IgM and release large, spherical IgM complexes. The complexes (termed “spherons”) reach 2 μm in diameter, detach from the cell surface, and settle out of solution. The spherons contain IgM multimers that incorporate the J chain and resist degradation by endoglycosidase H, arguing for IgM passage through the Golgi. Treatment of cells with inhibitors of proteoglycan synthesis, or incubation of spherons with chondroitinase ABC, degrades spherons, indicating that spheron formation and growth depend on interactions between IgM and glycosaminoglycans. This inference is supported by direct binding of IgM to heparin and hyaluronic acid. We conclude that, as a consequence of IgM binding to glycosaminoglycans, multivalent IgM–glycan complexes form in transit of IgM to the cell surface. Intra-Golgi formation of immune complexes could represent a new pathogenic mechanism for immune complex deposition disorders.

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“…Although local response to radiotherapy is very good [7][8][9][10] , about half of patients with SPs eventually develop a multiple myeloma [11][12][13][14][15][16][17] . Prescription doses used to irradiate this type of tumors are discussed in the literature.…”

Section: Discussionmentioning

confidence: 99%

Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

Wiazzane

Chargari²,

Plancher³

et al. 2013

WJR

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AIM:To assess the feasibility of the combination of helical tomotherapy ® (HT) and a concurrent systemic targeted therapy in patients with solitary plasmacytoma (SP) with the aim to decrease toxicity while improving therapeutic efficacy. METHODS:Six patients with biologically, histologically, and radiologically confirmed SP were treated using HT and a systemic targeted treatment concomitantly. Total dose was 40 Gy/20 fractions. Four patients received 4 cycles of concurrent lenalidomide-dexamethasone combination and two patients were treated with concomitant bortezomib-dexamethasone. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. RESULTS:Five patients had a bone tumor and one patient had an isolated pancreatic mass. Five patients presented with pain, one had neurologic symptoms related to medullary compression, which was treated by an emergency surgery. Median age was 59.5 years (range, 50-74 years). All patients had initial positron emission tomography-computed tomographys, three patients had total body bone magnetic resonance imaging examination, and three patients had computed tomodensitometry scans. The toxicity profile was excellent with no higher than grade 1 toxicity. Four of the six patients experienced a partial radiological response, four had complete response on positions emission tomography and 5/6 patients experienced a complete relief of their symptoms 4 mo after treatment. At a median follow-up of 18 mo, 5/6 patients were controlled clinically, radiologically, and biologically.CONCLUSION: Using HT, we could deliver a highly conformal irradiation concurrently with a molecularly targeted therapy. This association yielded in a high response rate and a low toxicity. A prospective study with longer follow-up will help determining the true benefit of such strategy.

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Multiple Myeloma and Immunosecretory Disorders

Cited by 19 publications

References 49 publications

The role of the insulin-like growth factor 1 receptor axis in multiple myeloma

The role of the insulin-like growth factor 1 receptor axis in multiple myeloma

Intra-Golgi Formation of IgM–Glycosaminoglycan Complexes Promotes Ig Deposition

Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

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