Circulating hyaluronan in the myelofibrosis/osteomyelosclerosis syndrome and other myeloproliferative disorders

Abstract

The serum concentration of hyaluronan (HYA) was determined in 59 patients with various myeloproliferative disorders, including 33 patients with idiopathic myelofibrosis. In 18 patients the serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised serum HYA levels were seen in patients with active disease compared with age-matched healthy subjects, whereas no significant difference in serum HYA was seen between patients with stable disease and age-matched controls. Serum HYA concentrations correlated significantly with the leukocyte count (rho = 0.38; P less than 0.02) and with the serum concentration of PIIINP (rho = 0.50; P less than 0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations decreased in concert with declining leukocyte counts. These findings suggest that clonal expansion is accompanied by a bone marrow stromal reaction similar to the repair processes following injury to soft connective tissues. The relatively modest changes in serum HYA with frequent overlaps between patient categories and healthy subjects imply that the clinical utility of single determinations of serum HYA in the present disease groups is restrained. On the other hand, sequential measurements of HYA may provide a reflection of the myeloproliferative process in individual patients.

Serum Hyaluronic Acid Levels Are Altered in Acute Leukemia Patients: Potential Prognostic Implications

“…1). In earlier studies, considerably elevated serum HA values have been observed in AML [26], multiple myeloma [29], malignant lymphoma [30], myelofibrosis, and CML [31], and also in various nonhematological diseases [13]. These studies confirmed that elevated serum HA levels may accompany malignant diseases.…”

“…This is in agreement with the findings of Hasselbach et al [31] (age and leukocyte count), Dahl et al [28] (age and creatinine), and Maksoud et al [26], but in contrast with the findings of Hasselbach et al [30] who reported no correlation between serum HA and alanine aminotransferase, or alkaline phosphatase. Maksoud et al [26] reported an inverse correlation between serum HA and hemoglobin concentration and a positive correlation between serum HA and the percentage of blasts cells in bone marrow in patients with AML.…”

“…Alterations in the flow of hepatic blood or lymph may influence the kinetics of HA elimination [40]. Moreover, the malignant cells may themselves have the potential to produce and release HA, as proposed by Hasselbach et al [31]. …”

“…Although serum HA is often considered as a prognostic marker in a variety of human diseases [22] and tumors [23,24,25], there are only a few studies examining serum concentrations of HA in patients with hematological malignancies. These reports involve patients with acute myeloid leukemia (AML) [26], T-acute lymphoblastic leukemia [27], multiple myeloma [28,29], malignant lymphoma [30], active myeloproliferative disease, and chronic myelogenous leukemia (CML) [31]. …”

NF-κB as a Central Mediator in the Induction of TGF-β in Monocytes from Patients with Idiopathic Myelofibrosis: An Inflammatory Response Beyond the Realm of Homeostasis

“…Furthermore, hyaluronic acid, an ECM protein that is increased in IMF could interact with the adhesion molecule, CD44 to stimulate IMF monocytes (12). With respect to ECM protein-adhesion molecule interactions, the ubiquitous distribution of ECM proteins in IMF patient (20,21) may partly explain the in vivo activated state of IMF monocytes (18), shown in Fig. 1.…”