Additional file 1: of Chemerin is elevated in multiple myeloma patients and is expressed by stromal cells and pre-adipocytes

Figure S1. Expression of CCRL2 and CMKLR1 in primary myeloma cells (pMM, n = 24) and cell lines (n = 9) analyzed by qPCR. GAPDH was used as an endogenous control. (DOCX 51 kb

IGFBP levels and distribution in controls, MGUS and MM.

<p>A) Autoradiograph of two representative ¹²⁵I-IGF Western ligand blots displaying plasma samples from the circulation (PB) and bone marrow (BM) taken from MGUS and MM patients and control (CON) individuals. The two top bands appearing at 38 and 42 kDa represent IGFBP-3. B) Western immunoblot analysis using a monoclonal IGFBP-2 primary antibody, confirming the identity of the 32-kDa band as IGFBP-2. C) The IGFBP disease to control ratio in the circulation. D) The IGFBP disease to control ratio in the bone marrow. E) Tissue distribution of the IGFBPs shown as the circulation to bone marrow ratio. * p<0.05, ** p<0.01, *** p<0.001</p

Patient characteristics.

<p>Patient characteristics.</p

Schematic overview of IGF and IGFBP levels in controls, MGUS and MM patients.

<p><u>In Peripheral blood (PB):</u> The level of IGFBP-2 significantly increases in MGUS and MM patients compared to controls, while IGFBP-3 decreases. The total IGFBP level is similar between MGUS, MM patients and control samples. <u>In Bone marrow (BM):</u> IGFBP-2 is significanlty increased in MM patients and IGFBP-3 is decreased in MGUS and MM patients. Total IGFBPs are lower in MGUS and MM patients. <u>Tissue distribution:</u> Total IGF1 and -2, IGFBP-2, IGFBP-3, and total IGFBP are distributed equally between the PB and BM in control individuals. In MGUS and MM patients, there are lower levels of IGFBP-2 and total IGFBP in the BM compared to PB. IGF1 and -2, and IGFBP-3 are equally distributed between compartments.</p

Total IGF1 and IGF2 levels in controls and patients with MGUS or MM.

<p>Levels of IGF1 measured by ELISA (A, B) and IGF2 (E, F) in plasma from circulation (A, E) and bone marrow (B, F). Correlation analysis of IGF1 (C) and IGF2 (G) between bone marrow and circulation. Mean pairwise ratio of bone marrow to circulating (for each individual) IGF1 (D) and IGF2 (H). Dots represent individual patients. Bars indicate standard deviations. (r) Pearson´s correlation coefficient. * p<0.01 compared to control.</p

Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population

<div><p>Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma Registry representing the entire MM population in Denmark from 2005–2013. Two-thousand two hundred and fifty three patients (90%) presented with reduction below lower normal levels of at least one uninvolved immunoglobulin. Using multivariable Cox regression we found that high age, high ISS score, high LDH and IgA MM were associated to both shorter overall survival and progression free survival. Furthermore, bone marrow plasma cell % was associated to short progression free survival. Immunoparesis had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)). Likewise, the number of suppressed immunoglobulins or the relative degree of suppressed uninvolved immunoglobulins from lower normal level (quantitative immunoparesis) was not associated to OS in the multivariable analysis. However, quantitative immunoparesis with at least 25% reduction (from lower normal level) of uninvolved immunoglobulins was associated to shorter PFS for the entire population. The impact of quantitative immunoparesis on PFS was present irrespective of calendar periods 2005–2008 and 2009–2013. Our population-based study does not confirm that immunoparesis at diagnosis is an independent prognostic factor regarding OS. However, quantitative immunoparesis is associated to a shorter PFS.</p></div

Multivariable analysis of factors for PFS.

<p>Multivariable analysis of factors for PFS.</p

Immunoparesis and association to OS and PFS in different age groups.

<p>Immunoparesis and association to OS and PFS in different age groups.</p

Multivariable analysis of factors for OS.

<p>Multivariable analysis of factors for OS.</p

Multivariable analysis of both qualitative and quantitative immunoparesis as risk factors for OS and PFS in all patients.

<p>Multivariable analysis of both qualitative and quantitative immunoparesis as risk factors for OS and PFS in all patients.</p