In VivoMurine Model of Leukemia Cell-Induced Spinal Bone Destruction

Abstract

Osteolytic bone lesions can be a consequence of leukemic bone infiltration or focal bone destruction by inflammatory factors released from leukemic cells. Destructive bone lesions have a negative impact on the quality of life of leukemia patients, causing unbearable pain and, in some cases, limb paralysis. However, the mechanism, by which leukemic cells produce destructive bone lesions, and the effect of therapeutics on osteolytic lesions have not been fully elucidated yet and, thus, stand to benefit from an in vivo model. To that end, HL-60 cells were transformed by retrovirus-mediated constitutively active (CA) STAT5 expression and injected into nonobese diabetic (NOD)/SCID mice via the tail vein. After three weeks, lumbar spines were subjected to histocytometric analysis. Xenograft mice developed hind limb paralysis in 2-3 weeks, which was consistent with the consequences of spinal bone destruction by extramedullary invasion of leukemia cells. The in vivo model will improve the understanding and treatment of osteolytic bone lesions caused by myeloid leukemic cells.

Targeting Acute Myeloid Leukemia Using Sphingosine Kinase 1 Inhibitor-Loaded Liposomes

“…MP-A08 liposomal treatment, despite administering at approximately a 100 times lower dose than MP-A08 as a free compound, significantly prolonged mouse survival (Figure ). In these survival studies, mice euthanasia was determined by animal welfare officers and experienced senior animal officers in accordance with the Institutional Animal Care, based on the severity of tumor burden resulting in >20% body-weight reduction or more severe suffering due to a fast clinical deterioration (such as hind limb paralysis, a condition where human leukemia cells infiltrate in the spleen, the bone marrow, and the spinal canal of the mice, resulting in spinal bone destruction , ). Collectively, the survival studies demonstrate that encapsulating MP-A08 in liposomes provides a suitable nanoscale carrier for intracellular delivery, increases drug uptake, enables feasibility of administering the novel antileukemic MP-A08 in vivo via intravenous injection, and has significant antileukemic activity.…”

Spontaneous and Induced Animal Models for Cancer Research

“…From another standpoint, intravenous injection can represent a reliable route for inducing leukemia. In this instance, protocols recommend an irradiation step using sub-lethal X-ray doses before proceeding with leukemia cells intravenous injection [150,151].…”