Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes

Mittelman, Moshe; Gardyn, Joseph; Carmel, Miri; Malovani, Hanna; Barak, Yigal; Nir, Uri

doi:10.1016/0145-2126(96)00002-1

Cited by 35 publications

(26 citation statements)

References 61 publications

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“…Iron deficiency appears to be a com mon cause [11,12,41], Intercurrent illness, infection or surgery may also decrease the response (patient 3) [5,11]. It is conceivable that at least some of the patients may not respond because of a defective Epo receptor [42], Future studies will have to focus on clarifying the patterns of response as well as overcome the resistance.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Mittelman¹,

Zeidman²,

Fradin³

et al. 1997

Acta Haematol

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Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated but inadequate erythropoietin (Epo) production appears to be important. This single-institute open-label, non-comparative clinical trial was undertaken in order to evaluate serum Epo levels in patients with MM and to study the efficacy and toxicity of recombinant human Epo (rHuEpo) in the treatment of MM-associated anemia. MM patients with a baseline hemoglobin (Hb) level of < 11 g/dl received rHuEpo 150 U/kg 3 times/week subcutaneously, with a possible dose increase to 300 U/kg if no response was observed after 4 weeks. The study was designed for 12 weeks, although some responders continued rHuEpo. The study endpoints were determined by an increase in Hb and a decrease in blood transfusion requirements (BTR). Seventeen patients were enrolled in the study. The median serum Epo level was 150 mU/ml (range 11-232). Four patients did not complete the study for reasons unrelated to rHuEpo, but to their underlying MM. Twelve patients (70.6%) responded with an increase in their Hb levels. One patient (5.9%) responded partially. The median Hb level rose from 9.4 g/dl (range 7.3-10.7) at study commencement to 12.5 g/dl (range 9.0-15.2). Six of the 11 patients who were transfusion dependent enjoyed a complete abolition of BTR. The response was also interpreted as an improved quality of life: 3 patients reported a decrease of 1 level in their WHO performance status (PS) score; in 8 patients, the PS declined by 2 grades and 1 patient enjoyed PS reduction by 4 scores. Six patients continue to receive rHuEpo up to 18 months, with a good response and a smaller maintenance dose. Four patients reported flu-like symptoms, 2 suffered from a local irritation and 1 experienced a transient controlled elevation of blood pressure. Summmary: (1) Pretreatment endogenous serum Epo levels were relatively low in all patients studied with MM-associated anemia; (2) rHuEpo was well tolerated in these patients; (3) rHuEpo was highly effective in the treatment of anemia in MM, and (4) the response to rHuEpo is characterized by an increase in Hb levels, a reduction in BTR and an improvement in the WHO PS score.

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Mittelman¹,

Zeidman²,

Fradin³

et al. 1997

Acta Haematol

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“…No apparent correlation was evident between the number of MDS cells coexpressing the EPO-R and CD34 or CD71-positive cells and impaired erythroid response, and MDS marrow cells expressed the full length EPO-R [9,11]. It was then postulated that intracellular structural defects of EPO-R, although not frequently analyzed and demonstrated [12], could cause defective receptor signaling following ligand binding [11]. In fact, STAT5-defective activation after EPO stimulation was observed in parallel with conserved STAT5 phosphorylation upon stimulation with IL-3, and this was attributed to a disturbance in an early stage of the EPO signal transduction pathway [9] (Figure 2).…”

Section: Biological Studiesmentioning

confidence: 99%

Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes

Santini

2011

The Oncologist

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“…In particular, the erythropoietin receptor is expressed at a normal density on MDS cells, but STAT5 activation in response to erythropoietin stimulation is defective (9). This observation was attributed to intracellular structural defects in the erythropoietin receptors of MDS cells, but this was not specifically showed (10,11). Few studies have been conducted regarding the basal activation of proliferative signaling in MDS marrow progenitors (9,12).…”

Section: Introductionmentioning

confidence: 99%

Distinct Signal Transduction Abnormalities and Erythropoietin Response in Bone Marrow Hematopoietic Cell Subpopulations of Myelodysplastic Syndrome Patients

Spinelli

Caporale²,

Buchi³

et al. 2012

Clinical Cancer Research

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Purpose: Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias as a result of ineffective hematopoiesis. Little is known about alterations in signal transduction pathways in MDS.Experimental Design: Multiparameter flow cytometry was used to evaluate the proteolytic activation of caspase-3 and the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and STAT5 specifically in defined CD34

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Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes

Cited by 35 publications

References 61 publications

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes

Distinct Signal Transduction Abnormalities and Erythropoietin Response in Bone Marrow Hematopoietic Cell Subpopulations of Myelodysplastic Syndrome Patients

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