Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25–60.9). Patients with high levels of sCD23 (>11.27, p = 0.026), sCD27 (>11.03, p = 0.04), SPINT1 (>1.6, p = 0.001), and LY9 (>8.22, p = 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients

Regulation of LFA-1 Expression by CD34 Positive Cells and Inducible Growth Factor Production by Stroma Enable Formation of Bone Marrow Compartments; Subject Heading

Leukocyte function associated antigen 1 (LFA-1) is an adhesion molecule indispensable in immune and inflammatory reactions, but its role in hematopoiesis is poorly understood. LFA-1 is considered as a marker of late stage stem cell maturation when expressed on CD34(+) bone marrow cells. We observed that CD34(+) bone marrow cells express LFA-1, that based on LFA-1 expression several subpopulations can be distinguished, and that the level of expression appeared highly variable among different donors. Unanticipated, in time course experiments we observed that CD34(+) LFA-1(-) cells expressed LFA-1 within 24 hours upon culture. These in vitro findings support the hypothesis that once contacts with bone marrow stroma are lost, LFA-1 is upregulated by default, due to the lack of negative regulating signals from stromal cells. This might also explain the widely variable expression of LFA-1 as a result of crowding of cells in the bone marrow with subsequent loss of contact with stroma and upregulation of LFA-1, thus equipping cells with adequate adhesion receptors to migrate throughout the bone marrow. Interestingly, the expression of the LFA-1 specific activation epitope L16 on these cells is low, even after culture. This demonstrated that LFA-1 is not activated, as was confirmed by low adhesion to ICAM-1. Activation of adhesion molecules is induced by several growth factors. Indeed, we show here that an osteoblastic cell line under normal conditions does hardly produce hematopoietic growth factors but these are rapidly induced after stimulation. Such rapid induction endows the bone marrow stroma with the property to modulate the adhesive strength and enabling migration through the different environments within the stroma. Prove for such compartments within the bone marrow is provided by histological data

Anemia in Hodgkin's lymphoma: the role of interleukin-6 and hepcidin.

Contains fulltext : 88183.pdf (publisher's version ) (Open Access)PURPOSE: Cytokines play a pivotal role in Hodgkin's lymphoma (HL). Because interleukin-6 (IL-6) induces expression of hepcidin, one of the principal regulators of iron metabolism, we studied the contribution of hepcidin in anemia in HL at diagnosis. PATIENTS AND METHODS: Plasma samples from 65 patients with HL were analyzed for hepcidin levels using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry; cytokine levels were analyzed using enzyme-linked immunosorbent assays and parameters of iron metabolism and acute-phase reaction. RESULTS: Hepcidin plasma levels were significantly higher in HL patients when compared with controls, independent of the presence of anemia (P = .001). In the subset of patients with anemia, hepcidin levels inversely correlated with hemoglobin levels (P = .01). Analyzing parameters of iron metabolism, hepcidin levels showed a positive correlation with ferritin (P 2 (P = .005). CONCLUSION: Our findings suggest that in HL, hepcidin is upregulated by IL-6. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic inflammation, although hepcidin-independent mechanisms contribute to development of anemia in HL

Proteomic markers with prognostic impact on outcome of chronic lymphocytic leukemia patients under chemo-immunotherapy: results from the HOVON 109 study

Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pretreatment and to search for new proteomic markers that might be related to treatment response in CLL. To this end, baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range: 1.25-60.9). Patients with high levels of sCD23 (>11.27, p= 0.026), sCD27 (>11.03, p= 0.04), SPINT1 (>1.6, p= 0.001), and LY9 (>8.22, p= 0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS differed between immunoglobulin heavy chain variable gene-mutated and unmutated patients, with the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients. (C) 2020 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved