In vivo induction of proteins during therapy of hairy cell leukemia with alpha-interferon.
نویسندگان
چکیده
The mechanism of the antineoplastic effect of interferon (IFN) is not known and may result from direct effects on the neoplastic cells themselves, activation of intermediary effector cells, or a combination of these effects. The synthesis of specific proteins is induced in hairy cells when they are exposed to alpha-IFN in vitro. In particular, the called p80, is markedly induced. We investigated this effect in the hairy cells of seven patients in the leukemic phase of hairy cell leukemia who were being treated with subcutaneous (SC) IFN alpha 2b (r-Hu-IFN-alpha 2). Polyacrylamide gel electrophoresis (PAGE) was carried out on [35S]methionine-labeled whole cell lysates visualized by autoradiography and silver staining. Within 2 days of starting IFN therapy, induction of specific protein synthesis, including p80 was seen by [35S]methionine labeling in freshly isolated circulating hairy cells from 6 of 6 patients tested. Therefore, alpha-IFN has a direct biochemical effect on hairy cells in vivo that is similar to in vitro effects, at least with regard to p80 synthesis, although the kinetics of this effect may vary in the two situations.
منابع مشابه
c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.
Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the onco...
متن کاملTreatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.
Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regression, with clinical improvement in a high percentage of cases. To investigate a...
متن کاملMechanism of interferon action in hairy cell leukemia: a model of effective cancer biotherapy.
Hairy cell leukemia (HCL) is one of the few malignancies for which alpha-interferon (IFN alpha) is considered effective first-line therapy. However, the mechanisms of action of this agent in vivo have been the subject of much debate; in particular, the issue of whether clinical improvement in IFN-alpha-treated HCL patients is dependent upon enhancement of host defenses or upon direct actions of...
متن کاملEffect of alpha-interferon therapy on bone marrow fibrosis in hairy cell leukemia.
Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month...
متن کاملInterferon-alpha downregulates the abnormal intracytoplasmic free calcium concentration of tumor cells in hairy cell leukemia.
Hairy cell leukemia (HCL) is a B-cell tumor affecting the preplasma stage of B-cell differentiation. One important feature of the disease is its exquisite sensitivity to interferon-alpha (IFN-alpha) therapy. Because we showed earlier that the CD20 molecule is consistently hyperphosphorylated in hairy cells and because previous studies showed that CD20 is involved in regulating intracytoplasmic ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 69 6 شماره
صفحات -
تاریخ انتشار 1987