Journal List > Korean J Lab Med > v.29(1) > 1011609

Lee, Kang, and Lee: The Analysis of Thrombopoietin and Clinical Parameters as a Marker for Disease Progression in Patients with Multiple Myeloma

Abstract

Background

Multiple myeloma (MM) causes the suppression of hematopoiesis because of malignant cells in the bone marrow. Thrombopoietin (TPO) is regulated by a feedback mechanism with platelets. Recently, it was suggested that an elevated TPO without thrombocytopenia was associated with impaired hematopoiesis. We evaluated whether TPO levels could be a marker for disease progression in MM.

Methods

The TPO levels were measured in 70 blood samples from 27 patients (newly/previously-diagnosed patients=13/14). We analyzed the TPO and clinical parameters, WBC, hemoglobin, creatinine, calcium, M-protein, protein, albumin, and β2-microglobulin. The TPO in 20 healthy controls ranged from 6 to 69 pg/mL.

Results

The TPO levels were significantly higher in MM patients with thrombocytopenia than in patients without thrombocytopenia and the healthy controls (median TPO: 293.0 pg/mL vs 59.6 pg/mL and 35.6 pg/mL, P<0.0001). There was a negative correlation between the TPO levels and the blood cells, i.e., leukocytes (r=-0.293), hemoglobin (r=-0.378) and platelets (r=-0.508) (P<0.05). Elevated TPO were found in association with normal platelet counts (N=20). Among the samples without thrombocytopenia, especially one year after the diagnosis, the hemoglobin (10.3 vs 12.9 g/dL, P=0.025) and albumin (3.3 vs 4.0 g/dL, P=0.085) were lower and the M-protein and protein tended to be higher in patients with elevated TPO compared to those with normal TPO.

Conclusions

Serum TPO was elevated with thrombocytopenia and related to impaired hematopoiesis. The elevated TPO without thrombocytopenia might be considered as impaired hematopoiesis and a marker for disease progression in patients with MM.

REFERENCES

1.de Sauvage FJ., Hass PE., Spencer SD., Malloy BE., Gurney AL., Spencer SA, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature. 1994. 369:533–8.
crossref
2.Lok S., Kaushansky K., Holly RD., Kuijper JL., Lofton-Day CE., Oort PJ, et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature. 1994. 369:565–8.
crossref
3.Bartley TD., Bogenberger J., Hunt P., Li YS., Lu HS., Martin F, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell. 1994. 77:1117–24.
4.Debili N., Wendling F., Cosman D., Titeux M., Florindo C., Dusanter-Fourt I, et al. The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets. Blood. 1995. 85:391–401.
crossref
5.Fielder PJ., Gurney AL., Stefanich E., Marian M., Moore MW., Carver-Moore K, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood. 1996. 87:2154–61.
crossref
6.Li J., Xia Y., Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999. 106:345–56.
crossref
7.Kuter DJ., Rosenberg RD. The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit. Blood. 1995. 85:2720–30.
crossref
8.Moller P., Andersson PO., Andersson AC., Wadenvik H. Plasma thrombopoietin concentrations in response to platelet transfusion therapy. Acta Haematol. 2000. 102:131–4.
crossref
9.Folman CC., de Jong SM., de Haas M., von dem Borne AE. Analysis of the kinetics of Tpo uptake during platelet transfusion. Transfusion. 2001. 41:517–21.
10.Folman CC., de Jong CM., de Haas M., von dem Borne AE. In multiple myeloma increased thrombopoietin (Tpo) production may be involved in the maintenance of platelet production. Eur J Haematol. 2001. 66:337–41.
crossref
11.Kunishima S., Tahara T., Kato T., Kobayashi S., Saito H., Naoe T. Serum thrombopoietin and plasma glycocalicin concentrations as useful diagnostic markers in thrombocytopenic disorders. Eur J Haematol. 1996. 57:68–71.
crossref
12.Kojima S., Matsuyama T., Kodera Y., Tahara T., Kato T. Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme-linked immunosorbent assay. Br J Haematol. 1997. 97:538–43.
crossref
13.Schrezenmeier H., Griesshammer M., Hornkohl A., Nichol JL., Hecht T., Heimpel H, et al. Thrombopoietin serum levels in patients with aplastic anaemia: correlation with platelet count and persistent elevation in remission. Br J Haematol. 1998. 100:571–6.
crossref
14.Emmons RV., Reid DM., Cohen RL., Meng G., Young NS., Dunbar CE, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood. 1996. 87:4068–71.
crossref
15.Chang M., Suen Y., Meng G., Buzby JS., Bussel J., Shen V, et al. Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production. Blood. 1996. 88:3354–62.
crossref
16.Meng YG., Martin TG., Peterson ML., Shuman MA., Cohen RL., Wong WL. Circulating thrombopoietin concentrations in thrombocytopenic patients, including cancer patients following chemotherapy, with or without peripheral blood progenitor cell transplantation. Br J Haematol. 1996. 95:535–41.
crossref
17.Kosugi S., Kurata Y., Tomiyama Y., Tahara T., Kato T., Tadokoro S, et al. Circulating thrombopoietin level in chronic immune thrombocytopenic purpura. Br J Haematol. 1996. 93:704–6.
crossref
18.Martin TG 3rd., Somberg KA., Meng YG., Cohen RL., Heid CA., de Sauvage FJ, et al. Thrombopoietin levels in patients with cirrhosis before and after orthotopic liver transplantation. Ann Intern Med. 1997. 127:285–8.
crossref
19.Shimazaki C., Inaba T., Uchiyama H., Sumikuma T., Kikuta T., Hirai H, et al. Serum thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 1997. 19:771–5.
crossref
20.Usuki K., Tahara T., Iki S., Endo M., Osawa M., Kitazume K, et al. Serum thrombopoietin level in various hematological diseases. Stem Cells. 1996. 14:558–65.
crossref
21.Durie BG., Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975. 36:842–54.
crossref
22.Zwierzina H., Rollinger-Holzinger I., Nuessler V., Herold M., Meng YG. Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes. Leukemia. 1998. 12:59–64.
crossref

Fig. 1.
The serum thrombopoietin level of healthy control and patients with multiple myeloma. The serum thrombopoietin level was not only significantly different among three groups (P<0.0001) by ANOVA but also between multiple myeloma with normal platelet and multiple myeloma with decreased platelet (P<0.001) by Mann-Whitney test.
kjlm-29-82f1.tif

Abbreviations: MM, multiple myeloma; N, sample size.

Table 1.
The Pearson correlation between thrombopoietin and clinical parameters
  Pearson correlation P value
Platelet -0.508 <0.001
Hemoglobin -0.378 0.001
Creatinine 0.331 0.007
White blood cell -0.293 0.014
M-protein 0.185 0.125
Total protein 0.137 0.258
β2-microglobulin -0.112 0.504
Albumin -0.032 0.795
Calcium -0.005 0.968
Table 2.
The analysis of clinical parameters according to the platelet count in patients with elevated thrombopoietin
  Platelet count ≤150 (×103/μL) (N=20) Platelet count >150 (×103/μL) (N=20) P value
Number of patients 10 11  
Sex (M/F) 16/4 15/5 1.000
Age (Median, yr) 68 (49-79) 62 (47-74) 0.358
M protein (g/dL) 3.8±0.6 2.2±0.4 0.025
Protein (g/dL) 8.9±0.5 7.5±0.4 0.032
White blood cell (×/μL) 4,923±588 6,166±486 0.111
Creatinine (mg/dL) 1.6±0.4 1.2±0.2 0.349
Hb (g/dL) 9.5±0.5 10.1±0.5 0.413
β2-microglobulin (mg/L) 6.4±2.7 4.6±1.2 0.611
Albumin (g/dL) 3.4±0.2 3.2±0.1 0.736
Calcium (mg/dL) 8.7±1.1 8.8±0.8 0.783

Mann-Whitney test.

Abbreviations: M, male; F, female; N, sample size.

Table 3.
The analysis of clinical parameters according to the thrombopoietin in blood samples with normal platelet at least 1 yr after the diagnosis of multiple myeloma
  Thrombopoietin ≤69 (pg/mL) (N=5) Thrombopoietin >69 (pg/mL) (N=17) P value
Number of patients 4 11  
Sex (M/F) 3/2 14/3 0.548
Age (Median, yr) 71 (54-75) 55 (47-74) 0.140
Hb (g/dL) 12.9±1.1 10.3±0.6 0.025
Albumin (g/dL) 4.0±0.3 3.3±0.1 0.085
M protein (g/dL) 0.9±0.1 2.0±0.5 0.493
Creatinine (mg/dL) 0.8±0.2 1.3±0.2 0.517
Calcium (mg/dL) 9.0±0.1 8.9±0.2 0.635
Protein (g/dL) 6.8±0.4 7.4±0.4 0.649
White blood cell (×/μL) 5,978±961 6,292±565 0.880
β2-microglobulin (mg/L) 4.1±0.1 5.1±1.7 1.000

Mann-Whitney test.

Abbreviations: M, male; F, female; N, sample size.

TOOLS
Similar articles