Zusammenfassung
Zur Prüfung der Frage, ob eine positive Korrelation zwischen dem Steroid-Rezeptorgehalt von Leukämiezellen und dem Erfolg einer Steroid-Therapie besteht, haben wir Glucocorticoid-Rezeptoren bei Leukämien und Lymphomen untersucht. Die Bestimmung erfolgte nach Baxter und Tomkins. Untersucht wurden 46 Patienten mit Leukämien und 18 Kontrollpersonen. Normale Lymphozyten haben durchschnittlich 3875 spezifische Bindungsstellen pro Zelle. Die Anzahl der Glucocorticoid-Rezeptoren in den Blasten von 17 Patienten mit akuter myeloischer Leukämie zeigten starke Schwankungen (Bereich 0 bis 15295 Rezeptoren pro Zelle). Sechs von 15 Patienten mit chronischer lymphatischer Leukämie wurden seit Jahren mit Glucocorticoiden behandelt und sprachen zur Zeit der Steroid-Rezeptor-Bestimmung auf diese Therapie nicht mehr an. Die Anzahl der Steroid-Bindungsstellen der Lymphozyten dieser Patienten erwies sich im Mittel als niedriger (2000 je Zelle) als bei den unbehandelten Patienten (4500 je Zelle). Bei 24 Patienten haben wir auch die In-Vitro-Sensitivität der Leukämiezellen gegenüber Dexamethason untersucht. Es konnte keine eindeutige Korrelation zwischen Rezeptorengehalt und In-Vitro-Sensitivität festgestellt werden. Weitere Analysen mit klinischen Daten weisen darauf hin, da\ die Bestimmung von Glucocorticoid-Rezeptoren für die Planung und Durchführung einer Therapie bei den lymphatischen Leukämien Bedeutung erlangen kann, jedoch wahrscheinlich nicht bei den myeloischen Leukämien.
Summary
In an attempt to investigate the utility of glucocorticoid receptor determination to predict clinical responsiveness in human leukemias we have studied glucocorticoid receptors in the leukemic cells from 46 patients and in the lymphocytes from 18 normal donors. In the normal lymphocytes there were 3,875 (Median) specific binding sites per cell. The blasts from 17 patients with ANLL had on average higher levels of binding sites per cell (Median = 7,250, range: 0 to 15,295) than the other leukemias. Of the 15 patients with CLL, six had received glucocorticoid treatment for 3 to 5 years. Their lymphocytes had lower number of receptors (Median = 2,000) than the other cases which were newly diagnosed (Median = 4,500). Four patients had ALL/AUL, three patients had blast crisis as terminal phase of CML, and seven had leukemic Non-Hodgkin lymphomas (Median = 3,500 sites/cell). In 24 patients we have also studied the in vitro sensitivity of the leukemic cells to dexamethasone. There was no marked correlation between glucocorticoid receptor levels and in vitro sensitivity. An attempt to correlate receptor levels with clinical responsiveness demonstrated that glucocorticoid receptor determination might be of value in patients with lymphoid malignancies but probably not in patients with other leukemias.
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Supported by the Tumorzentrum Heidelberg/Mannheim and Karl- und Maria-Biesinger-Stiftung, D-6932 Hirschhorn, Federal Republic of Germany
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Ho, A.D., Künstein, W. & Schmid, W. Glucocorticoid receptors and sensitivity in leukemias. Blut 42, 183–190 (1981). https://doi.org/10.1007/BF01026388
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DOI: https://doi.org/10.1007/BF01026388