Biochemical and immunological responses of hairy cell leukemia patients to interferonβ

Abstract

Ten hairy-cell leukemia patients were treated with interferon beta (IFN-beta) at a dose rate of 2 x 10(6) IU/m2 x 5 days for 4 weeks (induction therapy) and, thereafter, at the same dose three times a week for 11 months (maintenance therapy). The effect of this treatment on serum neopterin, beta 2-microglobulin, (2'-5')oligoadenylate [(2'-5')An] levels, intracellular (2'-5')An values and human Mx protein synthesis was analysed. There were significant rises in serum neopterin and (2'-5')An levels during both induction and maintenance, whereas beta 2-microglobulin levels rose only during induction. Rises in intracellular (2'-5')An were documented mainly during induction, but they were not significantly higher than pretherapy values. IFN beta provoked an increase in human Mx protein synthesis over the entire induction-maintenance period, but was only significantly higher than baseline during induction. All markers proved useful for monitoring the effects of IFN beta dose schedules, but were not predictive of clinical outcome. Natural killer activity and IFN gamma production, which were initially defective, followed a different trend from that of the other factors studied, in that increases were documented only late in the course of therapy when the disease was already in remission.

In vitro culture of B-lymphocytes derived from epstein-barr-virus-associated posttransplant lymphoproliferative disease: Cytokine production and effect of interferon-alpha

“…Interferons have been described to have a direct antimitotic effect on several tumor cell lines (Chen et al, 1988;Liberati et al, 1990). These antiproliferative effects have been attributed to reduced c-myc gene expression in BL and to reduced synthesis of autocrine growth factors in hairy cell leukemia (Jonak et al, 1987~ Heslop et al, 1990.…”

The biology of hairy cell leukemia

“…The IFN-a receptors seem to fbnction normally on HC. Thus, the binding of IFN-a induces a rapid down-regulation of the receptor (201) and incubation of PBMNC from leukemic HCL patients or HCL cell lines in vitro with IFN (94,202) and PBMNC from IFN treated HCL patients in vivo (1,94,203,204) have uniformly shown a rapid induction of synthesis of some intracellular proteins and a down-regulation of others. This has been taken as evidence for a direct mechanism of action of IFN in HCL (94), and even though it is in agreement with a direct effect, the mere induction of changes in protein synthesis and activity perse is not necessarily connected to a growth inhibition.…”

“…This has been taken as evidence for a direct mechanism of action of IFN in HCL (94), and even though it is in agreement with a direct effect, the mere induction of changes in protein synthesis and activity perse is not necessarily connected to a growth inhibition. This is entirely dependent of the proteins induced, and even though some of these like 2-5A (178) and the human Mx homolog (179) are known, the nature of most of these proteins are unknown (1, 94,202,203). Underscoring this objection is the fact that induction of novel proteins is also seen with IFN-y, which is ineffective in HCL (94), and that IFN have been shown to induce proteins in other cell types without affecting their growth (205).…”

“…Since IFN is a wellknown activator of NK cells (216), a number of groups have evaluated the possibility that IFN acts through killing of HC by an increase in lymphokine activated killer (LAK) or NK cell activity. Most investigators have reported an increase in NK activity in the PB in some or all HCL patients upon IFN treatment (11,28,185,203,217,218). A few investigators have, however, found that some patients do not exhibit such an increase, or that an increase could be seen only in leukemic patients subsequent to the disappearance of HC in PB.…”

Interferon-α-Induced Biologic Modifications in Patients with Chronic Myelogenous Leukemia

“…Preparation ofperipheral blood mononuclear cells (PBMC) PBMC were obtained by Ficoll-Hypaque density centrifuga¬ tion as previously described (6) and resuspended in phosphate- and are expressed as nM and ng/liter, respectively. Intracellular and serum 2',5'A Dry pellets of 2 x IO6 cells were stored at -80°C and serum samples at -20°C until assayed.…”