Gaucher Cells in Chronic Myelocytic Leukemia: An Acquired Abnormality

Kattlove, Herman E.; Williams, Jeannine C.; Gaynor, Evelyn; Spivack, Morton; Bradley, Roy M.; Brady, Roscoe O.

doi:10.1182/blood.v33.2.379.379

Cited by 142 publications

(18 citation statements)

References 20 publications

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“…The Type 111 Gaucher heterozygotes had the same mean concentration as the controls, 11.8 pmol/l. Patients with myelogenous leukemia have Gaucher-like cells in their spleens (Albrecht 1966, Kattlove et al 1969) and therefore plasma from patients with so.…”

Section: Resultsmentioning

confidence: 99%

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: Significant differences between Type I and Type III

Nilsson¹,

Håk̈ansson²,

Dreborg

et al. 1982

Clinical Genetics

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A method was developed for the determination of cerebrosides in 1 ml of plasma or 1 ml of packed erythrocytes. At least 90% of the cerebroside fraction consisted of glucosylceramide. In the erythrocytes, nothing but glucosylceramide was identified. The method was applied to plasma samples from 25 controls, 34 Gaucher Type III obligate carriers, 16 Gaucher Type III patients, 7 Gaucher Type I patients and 7 patients with myelogenous or lymphatic leukemia, as well as to erythrocyte samples from 20 controls, 6 Gaucher Type III obligate carriers, 16 Gaucher Type III patients and 6 Gaucher Type I patients. The concentration of plasma cerebroside was 11.4±4.2 (S.D.) in controls, 11.8 ± 2.6 in Gaucher Type III carriers, 30.4 ± 7.7 in Gaucher Type III patients and 21.8 ± 6.7 μmol/l in Gaucher Type I patients. The Gaucher patients had Significantly increased (p <0.001) plasma cerebroside values, while the plasma cerebroside concentration of the leukemic patients was only slightly increased, 14.7 ± 5.7 μmol/l. In the packed erythrocyte pellet the corresponding values were: Controls 2.9 ± 0.7, Gaucher Type III carriers 2.9 ± 0.7, Gaucher Type III patients 9.2 ± 2.4 and Gaucher Type I patients 6.5 ± 2.7 μmol/l. The phospholipid concentration was the same in all the three Gaucher groups and was not significantly different from that in the controls.

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Section: Resultsmentioning

confidence: 99%

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: Significant differences between Type I and Type III

Nilsson¹,

Håk̈ansson²,

Dreborg

et al. 1982

Clinical Genetics

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“…An animal model (Kanfer et al 1975;Stephens et al 1978Stephens et al , 1979 and in vitro models for Gaucher disease have been produced by injecting mice or treating macrophages with conduritol B-epoxide, an irreversible inhibitor of glucosylceramide b-glucosidase, causing intracellular storage of endogenous glucosylceramide (Das et al 1987;Newburg et al 1986Newburg et al , 1988Yatziv et al 1988). However, in addition to endogenously synthesized glucosylceramide, storage material in Gaucher cells is also thought to originate from the turnover of exogenously derived lipids in cell membranes of phagocytosed red and white blood cells (Kattlove et al 1969). In our model system using a macrophage cell line and feeding red blood cell ghosts obtained from a patient with Gaucher disease, lipid storage would be expected to occur much more rapidly than in unfed cells and to more closely mimic the disease state.…”

mentioning

confidence: 99%

Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease

Schueler

Kolter

Kaneski

et al. 2004

J of Inher Metab Disea

105

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Gaucher disease, the most common sphingolipidosis, is caused by a decreased activity of glucosylceramide beta-glucosidase, resulting in the accumulation of glucosylceramide in macrophage-derived cells known as Gaucher cells. Much of the storage material is thought to originate from the turnover of cell membranes, such as phagocytosed red and white blood cells. In this study, an in vitro model of Gaucher disease was developed by treating the murine macrophage cell line J774 with a specific inhibitor of glucosylceramide beta-glucosidase, conduritol B-epoxide, and feeding red blood cell ghosts, in order to mimic the disease state. It was found in this model system that glucosylceramide beta-glucosidase activity could be reduced to about 11-15% of the normal control level before increased storage of glucosylceramide occurred. This in vitro system allows insight into the correlation between enzyme activity and lipid storage as predicted by the theory of residual enzyme activity that was proposed by Conzelmann and Sandhoff.

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“…These cells are lipid-laden macrophages with fine linear cytoplasmic striations. Similar cells are also observed in chronic myeloid leukemia [5][6][7][8] where they are called Pseudo-Gaucher cells. When examined by electron microscopy, typical Gaucher cells [9][10][11][12] and Pseudo-Gaucher cells in CML both contain cytoplasmatic sacs with inclusions which differ, however [13,14]; in CML, they are linear densities with a fibrillar pattern, whereas in Gaucher disease, they are long and twisted 300 to 400 Å wide tubes.…”

Section: Introductionmentioning

confidence: 63%

Coincidence of Gaucher's disease due to a private mutation and Ph′ positive chronic myeloid leukemia

et al. 1998

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We report the case of a 46-year-old female with coexisting type I Gaucher's disease and chronic myeloid leukemia (CML). The diagnosis of Gaucher's disease was made in early childhood by bone marrow biopsy and was recently confirmed by biochemical demonstration of reduced leukocyte beta-glucocerebrosidase activity and the presence of Gaucher cells in a bone marrow aspirate. We analyzed the patient's genomic DNA for the underlying glucocerebrosidase mutations and have found homozygosity for a C-->T transition in cDNA nucleotide 593 (159 Pro-->Leu), presently an undescribed mutation. After initiation of replacement therapy with alglucerase we observed a significant increase of the platelet count in our patient. The diagnosis of CML was based on standard hematological parameters and the detection of the Philadelphia chromosome (Ph). With intermittent treatment with busulfan the patient has remained in chronic phase for nine years. The patient suffered from hepatosplenomegaly and thrombocytopenia, both of which can be caused by Gaucher's disease and CML. The aggravation of skeletal manifestations of Gaucher's disease, which occurred at the time of diagnosis of CML, could be due to increased production of leukocyte-derived glucocerebrosides that were not appropriately degraded because of the genetic beta-glucocerebrosidase deficiency.

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Gaucher Cells in Chronic Myelocytic Leukemia: An Acquired Abnormality

Cited by 142 publications

References 20 publications

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: Significant differences between Type I and Type III

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: Significant differences between Type I and Type III

Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease

Coincidence of Gaucher's disease due to a private mutation and Ph′ positive chronic myeloid leukemia

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