Recombinant Human Erythropoietin Is Associated with Increased Overall Survival in Patients with Multiple Myeloma

Baz, Rachid; Walker, Esteban; Choueiri, T.K.; Jawde, Rony Abou; Brand, Catherine; McGowan, Bridget; Yiannaki, E.; Andresen, Steve; Hussein, Mohamad A.

doi:10.1159/000097464

Cited by 33 publications

(26 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies were led by the observation that multiple myeloma (MM) patients treated with rHuEPO for their anemia, exhibited prolonged survival and improved quality of life (Baz et al, 2007;Mittelman et al, 1997;Mittelman et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells

Lifshitz

Prutchi-Sagiv

Avneon

et al. 2009

Molecular Immunology

View full text Add to dashboard Cite

Erythropoietin (EPO) is the main hormone that promotes proliferation and differentiation of erythroid progenitor cells via binding to its surface receptor (EPO-R). Recent studies suggest that this hormone may affect also other cell types, besides the red blood cell lineage. We have previously demonstrated that the immune system is a target of EPO; however, the direct target cells of EPO, as well as the molecular mechanisms underlying its role as an immunomodulator, are unknown. Here we present evidence for functional effects of EPO on dendritic cells (DCs), which are known to initiate the immune response. In-vivo experiments in EPO-injected mice and in transgenic mice over-expressing human EPO showed an increased splenic DC population with a higher cell surface expression of CD80 and CD86. Further analysis based on mouse models, showed that DCs derived in-vitro from bone marrow (BM-DCs) express EPO-R mRNA. In-vitro stimulation of these DCs with recombinant human EPO enhanced viability, upregulated CD80, CD86 and MHC class II and augmented the secretion of IL-12. Biochemical analysis of EPO mediated signaling in the BM-DCs showed activation of the AKT, MAPK and NF-kappaB pathways. EPO stimulation of the BM-DCs led to Tyr-phosphorylation of STAT3. The inability to detect EPO mediated activation of STAT5 in the BM-DCs, suggests that in DCs, STAT3 may play a more important role than STAT5 in EPO-R signaling. Taken together, our data support the premise that DCs are direct targets of EPO, thereby providing an insight to the immunomodulatory functions of EPO.

show abstract

Section: Introductionmentioning

confidence: 99%

Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells

Lifshitz

Prutchi-Sagiv

Avneon

et al. 2009

Molecular Immunology

View full text Add to dashboard Cite

show abstract

“…Previous studies from these authors indicated that EPO may prolong survival in MM patients [8], and these results have been supported by other scientists [9]. The effect of EPO on MM was also reproduced in murine models, where EPO promotes the development of an effective and long-lasting anti-tumor specific immune response mediated via activated CD8 + T cells [10].…”

mentioning

confidence: 62%

Activities of erythropoietin on tumors: An immunological perspective

Ghezzi

Mengozzi

2007

Eur J Immunol

View full text Add to dashboard Cite

There is a growing interest in the non-erythropoietic, tissue-protective and restorative actions of erythropoietin (EPO). While studies in this field have indicated that EPO can ameliorate chemotherapy-induced peripheral neuropathy and cardiotoxicity, the issue whether EPO can positively or negatively affect cancer patients is a hot one. In this debate, many activities of EPO are being considered, including tissue/neuroprotection, angiogenesis, anti-inflammatory activity, growth promotion, and inhibition of apoptosis. However, few studies have explored the interactions of EPO with the immune system. A study in this issue of the European Journal of Immunology by Katz et al. adds one new piece to the puzzle by showing that EPO can stimulate B cell-mediated immunity.

show abstract

“…Epo use was associated with significantly reduced myeloma survival in one retrospective study, 2 whereas other studies showed that Epo caused myeloma regression in mice, 3 that Epo did not impair time to progression or overall survival in patients treated with melphalan and prednisone with or without bortezomib, 4 or that Epo improved survival. 5 Whether tumor epithelial and/or endothelial cells express functional Epo receptor (EpoR) is the subject of controversy. 6 The ability to unequivocally link tumor EpoR expression with Epo treatment and clinical outcomes would provide a means for directly testing the clinical significance of tumor EpoR expression.…”

Section: Evaluating Surface Erythropoietin Receptor In Multiple Myelomamentioning

confidence: 99%

“…Error bars represent the average deviation of duplicate determinations. (b) Staining with FAB307P or A82 plus a secondary PE antibody (red histograms), or the corresponding isotype controls (blue histograms) is shown in plasma cells from the bone marrow of patients with multiple myeloma (patients [1][2][3][4][5][6][7][8] or normal donors (N1-N3). Staining events are shown in gated plasma cells, which were identified on the basis of CD45, CD38, CD138, CD19, and CD56 expression.…”

Section: Evaluating Surface Erythropoietin Receptor In Multiple Myelomamentioning

confidence: 99%

“…4 Although some reports indicated an association between poor clinical outcome and low lymphocyte counts early after Haplo-HSCT, 5 there is no study directly addressing the impact of T-cell reconstitution on relapse in longitudinal cohorts of pediatric patients having received this type of allograft. This issue is particularly relevant as the development of a potent immunity towards newly encountered antigens, including many of the known tumor antigens, requires thymic generation of naïve T cells with a broad specificity.…”

Section: Conflict Of Interestmentioning

confidence: 99%

See 1 more Smart Citation

Evaluating surface erythropoietin receptor in multiple myeloma

et al. 2012

View full text Add to dashboard Cite

In conclusion, our analysis in acute leukemia revealed mutations in the histone-modifying enzymes recently identified to be altered in other cancers, particularly UTX in ALL and MLL2 in AML, although not at a high incidence. Important to note is that UTX and MLL2 are part of the same protein complex and both MLL2 and UTX mutations may lead to similar phenotypic consequences in cancer cells. Also, MLL2 was not fully sequenced in our analysis, leaving open the possibility of additional mutations in AML. Nevertheless, our findings warrant further analyses within larger studies and most likely more comprehensive studies based on targeted or whole genome/exome next-generation sequencing approaches. Of interest, most of the UTX mutations observed in our study were found in clinically defined high-risk patients and at least 1 of those patients (05-046) eventually relapsed. Therefore, this observation might be of particular interest with regard to potential epigenetic treatment approaches, although the exact mechanisms of transformation in UTX-mutated ALL remain to be elucidated.

show abstract

Recombinant Human Erythropoietin Is Associated with Increased Overall Survival in Patients with Multiple Myeloma

Cited by 33 publications

References 41 publications

Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells

Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells

Activities of erythropoietin on tumors: An immunological perspective

Evaluating surface erythropoietin receptor in multiple myeloma

Contact Info

Product

Resources

About