Osteolytic Bone Resorption in Adult T-cell Leukemia/lymphoma

Overview

Journal Leuk Lymphoma

Specialties Hematology
Oncology

Date 2010 Mar 11

PMID 20214446

Citations 20

Authors

Sherry T Shu

Chelsea K Martin

Nanda K Thudi

Wessel P Dirksen

Thomas J Rosol

Affiliations

Soon will be listed here.

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is caused by human T lymphotropic virus type 1 (HTLV-1). Patients with ATLL frequently develop humoral hypercalcemia of malignancy (HHM) resulting from increased osteoclastic bone resorption. Our goal was to investigate the mechanisms of ATLL-induced osteoclastic bone resorption. Murine calvaria co-cultured with HTLV-1-infected cells directly or conditioned media from cell cultures had increased osteoclast activity that was dependent on RANKL, indicating that factors secreted from ATLL cells had a stimulatory effect on bone resorption. Factors released from resorbing bone stimulated proliferation of HTLV-1-infected T-cells. Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1alpha (MIP-1alpha), both osteoclast stimulators, were expressed in HTLV-1-infected T-cell lines. Interestingly, when HTLV-1-infected T-cells were co-cultured with pre-osteoblasts, the expression of osteoprotegerin (OPG), an osteoclast inhibitory factor, was significantly down-regulated in the pre-osteoblasts. When OPG was added into the ex vivo osteoclastogenesis assay induced by HTLV-1-infected T-cells, osteoclastogenesis was strongly inhibited. In addition, HTLV-1-infected T-cells inhibited expression of early osteoblast genes and induced late genes. These regulators will serve as future therapeutic targets for the treatments of HHM in ATLL.

Citing Articles

HTLV-1 infected T cells cause bone loss via small extracellular vesicles.

Pokhrel N, Panfil A, Habib H, Seeniraj S, Joseph A, Rauch D J Extracell Vesicles. 2024; 13(10):e12516.

PMID: 39385703 PMC: 11464911. DOI: 10.1002/jev2.12516.

The Effect of a Histone Deacetylase Inhibitor (AR-42) and Zoledronic Acid on Adult T-Cell Leukemia/Lymphoma Osteolytic Bone Tumors.

Elshafae S, Kohart N, Breitbach J, Hildreth 3rd B, Rosol T Cancers (Basel). 2021; 13(20).

PMID: 34680215 PMC: 8533796. DOI: 10.3390/cancers13205066.

In Vivo Tumorigenesis, Osteolytic Sarcomas, and Tumorigenic Cell Lines from Transgenic Mice Expressing the Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Viral Oncogene.

Lanigan L, Hildreth 3rd B, Dirksen W, Simmons J, Martin C, Werbeck J Am J Pathol. 2020; 191(2):335-352.

PMID: 33181139 PMC: 7863134. DOI: 10.1016/j.ajpath.2020.10.014.

Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone.

Kohart N, Elshafae S, Supsahvad W, Alasonyalilar-Demirer A, Panfil A, Xiang J J Bone Oncol. 2019; 19:100257.

PMID: 31871882 PMC: 6911918. DOI: 10.1016/j.jbo.2019.100257.

Parathyroid hormone-related protein promotes bone loss in T-cell leukemia as well as in solid tumors.

Kohart N, Elshafae S, Demirer A, Dirksen W, Breitbach J, Shu S Leuk Lymphoma. 2019; 61(2):409-419.

PMID: 31592701 PMC: 7032642. DOI: 10.1080/10428194.2019.1672055.

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