Serum beta 2 microglobulin in adult myeloid acute leukemias

Abstract

Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses.

β2-Microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells

“…[12][13][14][15] Based on the results that DCs differentiated from monocytes in the presence of high concentrations of ␤ 2 M had an impaired antigenpresenting capacity and induced a compromised type 1 T-cell response, our findings may be compatible with the clinical arena seen in these conditions. The abnormalities may be attributed to the failure in the up-regulation of surface expression of MHC class 1 antigen, costimulatory molecule CD80 and adhesion molecule CD54 on the cells, and high amounts of IL-6 and IL-10 and low amounts of IL-12 secreted by the cells.…”

“…These represent the normal levels of ␤ 2 M in healthy persons 5,6 and elevated levels under pathologic conditions. [7][8][9][10][11][12][13][14][15] According to the data collected in our Institute from more than 1000 myeloma patients, serum ␤ 2 M can be as high as 80 mg/L (80 g/mL). One might expect much higher concentrations of ␤ 2 M in tumor sites.…”

“…Selection of the concentration of 20 g/mL ␤ 2 M for these and other experiments in this study was based on our preliminary tests (data not shown), the results depicted in Figure 1B, and the commonly found serum levels of ␤ 2 M under pathologic conditions. [7][8][9][10][11][12][13][14][15] After culture, cells were washed 3 times and stained with the antibodies. As shown by the representative histograms of flow cytometry analysis of MoDCs with recombinant ␤ 2 M on day 7 (Figure 2), surface expression of CD1a, CD40, CD54, CD80, and HLA-ABC molecules was significantly (1.5-to 10-fold; P Ͻ .05 and P Ͻ 0.01) lower on ␤ 2 Mtreated cells.…”

“…4 In healthy persons, the serum concentration of ␤ 2 M is usually less than 2 mg/L, and the urinary excretion is less than 400 g/24 hours. 5,6 Two of the common features among diseases such as human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), 7,8 autoimmune disorders such as rheumatoid arthritis 9,10 and Sjögren syndrome, 11 and hematologic malignancies including multiple myeloma, lymphoma, and leukemia, [12][13][14][15] are elevated serum levels of ␤ 2 M and activation or inhibition of the immune system. In persons infected with HIV, high levels of serum ␤ 2 M correlate with the progression to AIDS, 7,8 whereas in the hematologic malignancies, the levels correlate with poor prognosis.…”

“…In persons infected with HIV, high levels of serum ␤ 2 M correlate with the progression to AIDS, 7,8 whereas in the hematologic malignancies, the levels correlate with poor prognosis. 13,14 Thus, based on the importance of ␤ 2 M under physiologic and pathologic conditions, we hypothesized that ␤ 2 M is not only a surrogate for viral or tumor burdens or a byproduct of immune activation but, at high concentrations, may have negative effects on the immune system. Dendritic cells (DCs) serve as the sentinels of the immune system (for review, see Banchereau and Steinman 16 ).…”