Interleukin‐11 as an osteoprotegerin‐inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis

Abstract

We came across a rare case of acute megakaryocytic leukemia, the clinical course of which was relatively chronic and nonaggressive. This case was complicated with generalized severe osteosclerosis (OS). The medium in which blastic cells from the patient were cultured showed a strong activity to enhance the expression of an osteosclerotic cytokine, osteoprotegerin (OPG), as revealed by real-time quantitative RT-PCR and Western blot analysis. The OPG-inducing activity of the culture medium was neutralized by the anti-interleukin-11 (IL-11) antibody. These results indicate that IL-11 produced by the blasts was a causative factor of the OS observed in this patient. Am.

Systemic osteosclerosis associated with primary bone marrow B‐cell lymphoma

“…Sato et al have reported a case of acute megakaryocytic leukemia with osteosclerosis showing that interleukin 11, a factor derived from leukemic cells, induced the expression of TA B L E 1 Reported cases of osteosclerosis associated with hematological malignancies in which the role of osteoprotegerin was examined Addition of the culture medium of the patient's leukemic cells enhanced the expression level of osteoprotegerin mRNA in human osteoblast MG63 cells, and this effect was abrogated by the pretreatment with anti-interleukin-11 neutralizing antibody in vitro. osteoprotegerin in osteoblast MG63 cells in vitro[5].Leung et al have reported a case of hairy cell leukemia with osteosclerosis with high serum osteoprotegerin levels[10]. The present case of PBML also showed an increase in serum osteoprotegerin levels.…”

Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

“…Increased number and/or function of megakaryocytes and platelets are commonly associated with myelofibrosis and are the likely key players in this pathologic process [ 16 ]. Cytokines from megakaryocytes and platelets appear to be necessary for fibrosis to occur [ 1 , 7 ]. Further studies have revealed a significant role of TGF-β in stimulating fibroblast collagen synthesis and pathologically increasing deposition of bone marrow stromal fibers [ 5 ].…”

“…The frequent association of trisomy 19 with acute megakaryoblastic leukemia suggests genes encoded or regulated by chromosome 19 play a role in megakaryoblastic proliferation [ 10 ]. Additionally, acute megakaryocytic leukemia with osteosclerosis has been shown to have increased levels of an osteosclerotic cytokine, osteoprotegerin (OPG) [ 7 ]. The induction of OPG was demonstrated to be due to interleukin-11 production by the leukemic blasts [ 7 ].…”

“…Additionally, acute megakaryocytic leukemia with osteosclerosis has been shown to have increased levels of an osteosclerotic cytokine, osteoprotegerin (OPG) [ 7 ]. The induction of OPG was demonstrated to be due to interleukin-11 production by the leukemic blasts [ 7 ]. The gene for interleukin-11 is located on chromosome 19 which may explain this association.…”

“…Marked osteosclerosis and myelofibrosis are often seen in cases of hematologic malignancy but are seen most commonly in myeloproliferative neoplasms and acute megakaryoblastic leukemia (FAB-M7) especially in pediatric populations [ 6 ]. It was reported that interleukin-11 (IL-11), which is secreted from blasts, acts as an osteoprotegerin (OPG) inducing factor in patients with acute megakaryocytic leukemia and may lead to osteosclerosis [ 7 ]. In addition, trisomy 19 is frequently present in both entities; however, a definitive association between osteosclerosis and trisomy 19 has not been described [ 8 ].…”