Stem Cells, Vol. 14, No. 3, 363-364,
May 1996
© 1996 AlphaMed Press
Macrophage Colony-Stimulating Factor Levels in the Plasma of Bone Marrow Aspirate in Several Hematological Malignancies
Y. Denizot,
P. Fixe,
F. Trimoreau,
V. Praloran
Laboratoire d'Hématologie Experimentale Faculté de Médecine 2 rue Dr. Marcland 87025 Limoges, France
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To the Editor:
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We read with interest the work of Shinohara et al. [1 ] reporting the levels of G-CSF in the plasma of the bone marrow (BM) aspirate in various hematological disorders. To assess whether BM plasma may be suitable to study other molecules, we have investigated the levels of M-CSF, also known as CSF-1 [2 ,3 ], in the BM plasma of patients with lymphoid and nonlymphoid hematological malignancies.
Using our collection of plasma BM samples [4 ], M-CSF levels were measured in 24 patients with a lymphoid malignancy including ten multiple myeloma (MM) (mean age 69 ± 3, sex ratio male/female 7:3), seven chronic lymphocytic leukemia (CLL) (mean age 70 ± 4, sex ratio 4:3), four non-Hodgkin's lymphoma (NHL) (mean age 77 ± 4, sex ratio 2:2), two Waldenström's macroglobulinemia (WM) (mean age 71 ± 2, sex ratio 1:1), and one acute lymphocytic leukemia (ALL) (age 63, one male). M-CSF levels were assessed in 14 patients with a nonlymphoid malignancy including six acute myeloid leukemia (AML) (mean age 68 ± 3, sex ratio 3:3), four refractory anemia with excess of blasts (RAEB) (mean age 67 ± 3, four males), two myeloproliferative syndrome (MS) (mean age 63 ± 1, two males), one chronic myeloid leukemia (CML) (age 76, one female), and one refractory anemia with ringed sideroblast (RARS) (age 73, one male). They were compared to 53 control subjects (mean age 72 ± 2, sex ratio 26:27). M-CSF levels were measured with an enzyme-linked immunosorbent assay using the same rabbit polyclonal antibodies for the M-CSF capture and signal generation [5 ]. The sensitivity of the assay enables detection of M-CSF levels as low as 10 international units (IU) per ml (International standard at 6 x 104 IU/ml with 1 IU = 16 pg of glycosylated M-CSF, NIBSC; Potters Bar, UK). M-CSF concentrations were also assessed in blood plasma of 36 healthy controls (mean age 51 ± 4, sex ratio 19:17). Comparison between groups was made using Mann-Whitney U-test. Correlations between M-CSF levels in the BM plasma of controls and the percentage of erythroblasts, granulocytes, lymphocytes, plasmocytes and monocytes in the BM plasma samples were calculated by linear regression analysis.
In normal controls, BM plasma M-CSF levels (274.8 ± 21.1 IU/ml) were significantly higher (p = 0.02) than in blood plasma (198.3 ± 17.4 IU/ml). BM plasma M-CSF concentrations in patients with lymphoid and nonlymphoid malignancies are reported in Figure 1
. M-CSF levels were significantly lower (p = 0.02) in patients with lymphoid hematological malignancies but not with nonlymphoid malignancies (p = 0.21) compared to controls. The group of patients with a myeloma had lower M-CSF concentrations (p = 0.04) compared to controls. No correlation was found between M-CSF levels in the aspirate of the BM plasma of control (n = 53) and the percentage of granulocyte (r = 0.19, p = 0.62), erythroblast (r = 0.07, p = 0.62), lymphocyte (r = 0.23, p = 0.09), plasmocyte (r = 0.008, p = 0.95) and monocyte (r = 0.02, p = 0.86) in the aspirate.
M-CSF is measurable in BM plasma at biologically active concentrations. As reported for G-CSF [1 ], higher M-CSF levels in the normal BM plasma compared to blood plasma may be linked to a local M-CSF production by cells of the BM environment [2 ,3 ]. Another possibility is that M-CSF could be anchored as a proteoglycan form in the extracellular matrix [3,6 ]. When compared to M-CSF BM levels in normal controls, those in patients with myeloma were lower while those of patients with other hematological malignancies were not different. At the present time, the clinical usefulness and significance of these low M-CSF concentrations in the BM plasma of myeloma patients require further evaluation. Our results strengthen the work of Shinohara et al. [1 ], which suggests that as cytokines work locally, their assessment in the BM plasma may more directly reflect the pathophysiological mechanisms of hematological disorders than do those in the peripheral blood plasma. Clearly new areas of investigation are open for several other potent molecules involved in the regulation of hematopoiesis such as interleukin 6 and GM-CSF.
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Acknowledgments
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This study is supported by grant number 6412 from the Association pour la Recherche contre le Cancer. P. Fixe is the recipient of a grant from the "Ligue Nationale Francaise Contre le Cancer" (Comité de la Haute Vienne).
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References
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Shinohara K, Oeda E, Nomiyama J et al. The levels of granulocyte colony-stimulating factor in the plasma of the bone marrow aspirate in various hematological disorders. STEMCELLS 1995;13:421–427.
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Praloran V. Structure, biosynthesis and biological roles of monocyte-macrophage colony stimulating factor (CSF-1 or M-CSF). Nouv Rev Fr Hematol 1991;33:323–333.
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Stanley RE, Berg KL, Einstein DB et al. The biology and action of colony stimulating factor-1. STEMCELLS 1994;12(suppl 1):15–25.
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Denizot Y, Trimoreau F, Dupuis F et al. PAF and haematopoiesis: III. Presence and metabolism of platelet-activating factor in human BM. Biochim Biophys Acta 1995;1265:55–60.[Medline]
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Coupey L, Gourbil A, Berrada L et al. Développement et mise au point d'un Elisa anti-M-CSF: aspects techniques et intérêt clinique potentiel en hématocancérologie. Bull Cancer 1992;79:569a.
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Suzu S, Ohtsuki T, Makishima M et al. Biological activity of a proteoglycan form of macrophage colony-stimulating factor and its binding to type V collagen. J Biol Chem 1992;267:16812–16815.[Abstract/Free Full Text]
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To the Editor:
References
): CLL; (
): MM; (
): NHL, ALL and WM. Nonlymphoid malignancies: (