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Mechanisms behind hypocholesterolaemia in hairy cell leukaemia

^a Division of Clinical Haematology and Oncology, Department of Medicine, Huddinge Hospital, Huddinge, Sweden, ^b Departments of Clinical Pharmacology and Oncology, Karolinska Hospital, Stockholm, Sweden

Correspondence to: Dr G Juliusson, Department of Haematology, University Hospital, S-581 85 Linkoping, Sweden.

Hypocholesterolaemia is a common finding in various malignant disorders, such as acute myeloid leukaemia, chronic myeloproliferative disorders, and carcinoma of the colon.¹ It is unclear whether it is a risk factor for the development of malignancy or secondary to the cancer.¹ In acute myeloid leukaemia hypocholesterolaemia is the result of an increased uptake of cholesterol by leukaemic cells,² as indicated by an inverse correlation between cholesterol concentration and the activity of low density lipoprotein receptors in leukaemic cells. Hypocholesterolaemia is uncommon in lymphoid tumours, such as lymphoma and chronic lymphocytic leukaemia, but has been observed in patients with hairy cell leukaemia³--a rare disease affecting middle aged men that is clinically characterised by cytopenia, splenomegaly, and impaired immunity and may be fatal after an infection.

Patients, methods, and results

To evaluate mechanisms behind the development of hypocholesterolaemia in patients with hairy cell leukaemia, we analysed serial serum lipid concentrations after treatment with 2-chlorodeoxyadenosine in 24 patients with active disease.⁴ Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglyceride concentrations all rose significantly after treatment (P<0.00001, P=0.00002, P=0.0001, and P=0.02, respectively). The figure shows the pattern for low density lipoprotein cholesterol concentration. The mean difference in low density lipoprotein cholesterol concentration from baseline values was 0.90 mmol/l (95% confidence interval 0.55 to 1.25 mmol/l) in 24 patients at three months (P<0.001) and 0.98 mmol/l (0.62 to 1.33 mmol/l) in 18 patients at six months (P<0.001). In one patient repeated serum cholesterol and haemoglobin concentrations before diagnosis showed that the hypocholesterolaemia developed in parallel with anaemia, a marker for hairy cell leukaemia.⁵

View larger version (22K): [in this window] [in a new window]   Median low density lipoprotein cholesterol concentrations with quartile and extreme values in patients with hairy cell leukaemia after 2-chlorodeoxyadenosine treatment

We also analysed low density lipoprotein receptor activity by the cellular degradation of low density lipoprotein labelled with iodine-125 in isolated blood mononuclear cells from 12 patients with circulating hairy cells.² Only one patient showed increased low density lipoprotein degradation, and this patient was not hypocholesterolaemic.

Comment

Hypolipidaemia, mainly due to a low concentration of low density lipoprotein cholesterol, is a frequent finding in advanced hairy cell leukaemia, but values revert to normal after successful treatment. Thus it is a disease related phenomenon and not a predisposing factor for tumour development. Hypocholesterolaemia in patients with active disease was not caused by low density lipoprotein receptors being more active in hairy cells than in normal blood leucocytes; this indicates that the disease mechanism is different in hairy cell leukaemia and acute myeloid leukaemia, in which leukaemic cells show increased uptake of cholesterol.²

The lipid concentrations were related to the size of the spleen,⁵ and hypocholesterolaemia is more common in patients with splenomegaly than in those with a normal sized spleen or those who have had a splenectomy. Hairy cell leukaemia may influence the lipid metabolism of the reticuloendothelial system through cytokines such as granulocyte-macrophage colony stimulating factor and platelet derived growth factor, both of which influence lipid metabolism.

1. Vitols S. Uptake of low density lipoprotein by malignant cells: possible therapeutic applications. Cancer Cells 1991;3:488-95. [Medline]
2. Vitols S, Gahrton G, Bjorkholm M, Peterson C. Hypocholesterolaemia in malignancy due to elevated low density lipoprotein receptor activity in tumour cells: evidence from studies in patients with leukaemia. Lancet 1985;ii:1150-4.
3. Hakimian D, Tallman M, Koslow D, Rademaker A. Hypocholesterolaemia in patients with hairy cell leukaemia: a potential marker for malignant cell proliferation. Blood 1991;78(suppl 1):454a.
4. Juliusson G. Liliemark J. Rapid recovery from cytopenia in hairy cell leukaemia following treatment with 2-chloro-2'-deoxyadenosine (CdA): relation to opportunistic infections. Blood 1992;79:888-94. [Abstract/Free Full Text]
5. Juliusson G, Vitols S, Liliemark J. Disease-related hypocholesterolemia in patients with hairy cell leukemia: correlation to spleen size but not to tumor cell burden or low-density lipoprotein activity. Cancer. (In press.)

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Relevant Article

Hypocholesterolaemia in hairy cell leukaemia

John Hinnie and Dennis Stj O'Reilly
BMJ 1995 311: 1437. [Extract] [Full Text]

This article has been cited by other articles:

• Hinnie, J., O'Reilly, D. S. (1995). Hypocholesterolaemia in hairy cell leukaemia. BMJ 311: 1437b-1437 [Full text]