Ultrastructural, immunologic and clinical follow-up of five patients with HCL treated with interferon (IFN) for more than three years.
BACKGROUND
Treatment results in HCl have been improved by the use of alpha-IFN, which is now the standard first-line therapy for this disease, but the mechanism of IFN action is still unclear. It is known, however, that IFN is able to induce hematologic, immunological and phenotype membrane changes which parallel the patients' (pts) clinical response. The aim of our study was to correlate the clinical response to IFN treatment with ultrastructural and phenotype membrane changes in hairy cells (HCs), in order to elucidate the mechanism of IFN action at the cell level.


METHODS
We assessed the phenotype membrane and ultrastructural changes induced in HCs by long-term alpha-IFN treatment in five pts with HCL; membrane-bound Il 2-R on PHA-stimulated PBL, the release of IL 2-R by PHA-stimulated PBL and the serum levels of s-IL 2-R were also determined in one pt.


RESULTS
The surface immunological phenotype, mainly the HCL-related surface antigen CD25, changed after IFN treatment, dropping from abnormally high to normal values. Furthermore, IFN treatment induced ultrastructural changes in HCs, consisting mainly of a sharp reduction in, up to the almost complete disappearance of, the hairy projections: very few, if any, short, thick villi persisted. The ultrastructural changes in HCs paralleled clinical and hematologic response to IFN treatment in such a way that IFN alone may be considered the cause of these changes. As far as detection of the membrane-bound IL 2-R p55 chain on PHA-stimulated PBL is concerned, the expression of p55 is very high on the membrane of HCs; a high level of serum s-IL 2-R was also found in the HCL pt studied before IFN treatment, whereas the release of IL 2-R by PHA-stimulated PBL was higher than normal, but not significantly. Two of our pts, who did not respond or responded very poorly clinically to IFN treatment, should probably be considered cases of HCL "variants".


CONCLUSIONS
The phenotype membrane and the ultrastructural changes in HCs very closely paralleled the patients' clinical responses to IFN, suggesting that both the immunologic and the morphologic changes induced in HCs by in vivo IFN treatment are a direct counterpart of its biologic effect.
Mantovani
G
G
Istituto di Medicina Interna, Università di Cagliari, Italy.
Astara
G
G
Curreli
L
L
Lai
P
P
Turnu
E
E
Locci
F
F
Lantini
M S
MS
Cossu
M
M
Riva
A
A
Del Giacco
G S
GS
D000368:Aged; D001402:B-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000473:pathology / Q000628:therapy*; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins; D012074:Remission Induction
D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins