Eosinophilic Crystals as a Distinctive Morphologic Feature of a Hyaline Droplet Nephropathy in a Mouse Model of Acute Myelogenous Leukaemia

Abstract

Eosinophilic crystals have been described in the upper and lower respiratory tract, gall bladder, intrahepatic bile ducts and glandular stomach of different laboratory mice strains. They have been recently identified as chitinase-like (Ym1/Ym2) proteins. Here we describe the occurrence of eosinophilic crystals in the renal tubules of mice with experimentally induced acute myelogenous leukaemia. Fourteen FVB/N and 29 129Sv mice of both sexes, 8-10 weeks of age, were employed to establish a model of human acute myelogenous leukaemia. Nine mice that developed a widespread acute myelogenous leukaemia revealed the presence of eosinophilic crystals in renal tubules. The presence of eosinophilic crystals in the kidneys was constantly associated with a hyaline droplet nephropathy. Immunohistochemistry showed that the crystals and the hyaline droplets were composed of chitinase-like (Ym1/Ym2) proteins. Furthermore, immunoreactivity for Ym1/Ym2 proteins was also detected in the crystalline material stored in the cytoplasm of large macrophage-like cells or in extracellular localization within the leukaemic infiltrates. On the basis of our results we hypothesize that the detection of the Ym1/Ym2 proteins in the urine of mice might represent a feasible indicator of the burden and progression of the leukaemic condition in our murine model.

PML-RARα and Dnmt3a1 Cooperate in vivo to Promote Acute Promyelocytic Leukemia

“…In primary mice, overexpression of PML-RARα and Dnmt3a1 resulted in early death secondary to an eosinophilic infiltrate that consolidated the lungs, leading to death before progression to leukemia. Such an infiltrate has been previously described in the PML-RARα model (19) and was seen infrequently in PR-alone mice in this study. However, it was dramatically enhanced in the PR+Dnmt3a1 mice.…”

Immmunophenotype of Spontaneous Hematolymphoid Tumors Occurring in Young and Aging Female CD-1 Mice

“…Cytoplasmic lysozyme droplets have been reported to accumulate in the renal tubules of Wistar-Frith rats injected intraperitoneally with rat myeloid leukemia (choroleukemic) cells (Klockars et al, 1974). YM1 and YM2 chitinase-like lectins have been reported to accumulate as eosinophilic droplets in renal tubules of a mouse with experimental myeloid leukemia (Marchesi et al, 2003; Marchesi et al, 2006). In the latter report the renal tubular eosinophilic droplets co-expressed YM1 protein and lysozyme, but the myeloid tumor cells in this single case did not express lysozyme suggesting the myeloid tumor cells were not the source of the lysozyme.…”

Proceedings of the 2012 National Toxicology Program Satellite Symposium

“…Further, Chi3l3 is thought to play a role in mediating cell–cell and cell–matrix interactions, including those associated with tissue damage, repair, and remodeling because it binds various polysaccharides and glycosaminoglycans involved in extracellular matrix remodeling and tissue repair (Nio et al 2004; Waern et al 2010). Other investigators have postulated that it may contribute to hematopoiesis, since it is expressed in the fetal liver and adult hematopoietic tissue including the spleen and bone marrow and has been associated with crystal formation in a mouse model of myeloid leukemia (Marchesi et al 2003). …”