High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

[Lithium treatment and hyperparathyroidism]. / Litiumbehandling og hyperparatyreoidisme.

BACKGROUND: Lithium treatment, which is extensively used in bipolar affective disorders, may give rise to hypercalcaemia and sometimes to irreversible hyperparathyroidism. MATERIAL AND METHODS: We present a patient who developed hyperparathyroidism following long-term treatment with lithium. RESULTS: After 15 years on lithium the patient was diagnosed with hypercalcaemia; at the same time the patient stopped her lithium medication. Two years later she developed depression with psychotic symptoms and was given electroconvulsive treatment. Measurements of serum calcium and parathormon showed that she had developed hyperparathyroidism. Neck exploration was performed, and two parathyroid adenomas (weight 650 mg and 880 mg), which had been detected by scintigraphy, were removed. Lithium treatment was restarted. One year later she was normocalcaemic and her mood was normal. INTERPRETATION: In lithium-induced hyperparamyroidism, lithium should be replaced with other mood stabilizers, preferably an antiepilepticum. If cessation of lithium therapy does not lead to normocalcaemia, parathyroidectomy is indicated.

[Methemoglobinemia--causes, diagnosis and treatment]. / Methemoglobinemi--årsaker, diagnostikk og behandling.

BACKGROUND: Methaemoglobinaemia is an infrequent condition. It can be congenital or be induced by several toxic compounds. In methaemoglobin (metHb) the iron in the haem moiety of haemoglobin is oxidized from the ferrous (Fe2+) to the ferric state (Fe3+). This complex is dark brown and unable to transport oxygen. Combined with a leftward shift in the oxyhaemoglobin dissociation curve this leads to decreased tissue oxygenation with subsequent hypoxic features in patients. CASE REPORTS: We report two cases of dapsone-induced methaemoglobinaemia. The blood, mucosa and nail beds adopted a brown-bluish appearance which was used diagnostically. One patient was treated effectively with repeated injections of methylene blue, which reduces methaemoglobin. In the other patient, the methaemoglobin level declined with a T50 of 50 hours. Both patients had few symptoms and made an uneventful recovery. INTERPRETATION: The hypoxia in methaemoglobinaemia may be effectively treated with methylene blue. Repeated injections may be necessary.