Serum soluble IL-2 receptor as a tumor marker in patients with hairy cell leukemia

Abstract Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2′-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.

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Serum soluble IL-2 receptor as a tumor marker in patients with hairy cell leukemia

Blood ◽

10.1182/blood.v71.5.1304.bloodjournal7151304 ◽

1988 ◽

Vol 71 (5) ◽

pp. 1304-1309 ◽

Cited By ~ 2

Author(s):

RG Steis ◽

L Marcon ◽

J Clark ◽

W Urba ◽

DL Longo ◽

...

Keyword(s):

Cell Membrane ◽

Interferon Alpha ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Response To Therapy ◽

Soluble Form ◽

Hairy Cell ◽

Cell Leukemia ◽

Activated T Cells ◽

Recombinant Interferon

Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2′-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.

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Effective natural interferon-alpha therapy in recombinant interferon- alpha-resistant patients with hairy cell leukemia

Blood ◽

10.1182/blood.v78.1.38.38 ◽

1991 ◽

Vol 78 (1) ◽

pp. 38-43 ◽

Cited By ~ 55

Author(s):

P von Wussow ◽

H Pralle ◽

HK Hochkeppel ◽

D Jakschies ◽

S Sonnen ◽

...

Keyword(s):

Interferon Alpha ◽

Hairy Cell Leukemia ◽

Mononuclear Cells ◽

Hairy Cell ◽

Cell Leukemia ◽

Recombinant Interferon ◽

Homologous Protein ◽

Ifn Alpha ◽

Interferon Alpha Therapy ◽

Alpha Therapy

Abstract To explore the relationship between anti-interferon-alpha (anti-IFN- alpha) antibodies and loss of clinical responsiveness to IFN-alpha treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2 years of therapy, 10 patients developed rIFN-alpha- 2a-neutralizing and 15 rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rIFN-alpha-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN- induced Mx-homologous protein in mononuclear cells after a single injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight of the nine resistant rIFN-alpha patients were found to be highly specific for rIFN-alpha-2a. Therefore, these eight patients were switched to natural IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-alpha, achieving durable objective responses similar to those obtained previously with rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha antibody-positive patients can effectively be treated with nIFN-alpha.

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Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity

Blood ◽

10.1182/blood.v70.5.1530.1530 ◽

1987 ◽

Vol 70 (5) ◽

pp. 1530-1535 ◽

Cited By ~ 72

Author(s):

M Chilosi ◽

G Semenzato ◽

G Cetto ◽

A Ambrosetti ◽

L Fiore-Donati ◽

...

Keyword(s):

Natural Killer ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Alpha Interferon ◽

Soluble Form ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Mediated Immunity ◽

Hairy Cell ◽

Cell Leukemia

Abstract In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

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Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alpha-2A [letter; comment]

Blood ◽

10.1182/blood.v76.5.1055.bloodjournal7651055 ◽

1990 ◽

Vol 76 (5) ◽

pp. 1055-1055

Author(s):

M Lishner ◽

R Lang

Keyword(s):

Interferon Alpha ◽

Hairy Cell Leukemia ◽

Hairy Cell ◽

Cell Leukemia ◽

Recombinant Interferon ◽

Long Term Follow Up ◽

Letter Comment ◽

Recombinant Interferon Alpha

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Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia [see comments]

Blood ◽

10.1182/blood.v76.10.1941.bloodjournal76101941 ◽

1990 ◽

Vol 76 (10) ◽

pp. 1941-1945 ◽

Cited By ~ 1

Author(s):

JM Richards ◽

R Mick ◽

JM Latta ◽

K Daly ◽

MJ Ratain ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Standard Dose ◽

Clinical Status ◽

Interleukin 2 ◽

Cell Lineage ◽

Disease Status ◽

Soluble Form ◽

Hairy Cell ◽

Cell Leukemia ◽

Serum Samples

Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty- seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated.

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Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity

Blood ◽

10.1182/blood.v70.5.1530.bloodjournal7051530 ◽

1987 ◽

Vol 70 (5) ◽

pp. 1530-1535

Author(s):

M Chilosi ◽

G Semenzato ◽

G Cetto ◽

A Ambrosetti ◽

L Fiore-Donati ◽

...

Keyword(s):

Natural Killer ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Alpha Interferon ◽

Soluble Form ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Mediated Immunity ◽

Hairy Cell ◽

Cell Leukemia

In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

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Effective natural interferon-alpha therapy in recombinant interferon- alpha-resistant patients with hairy cell leukemia

Blood ◽

10.1182/blood.v78.1.38.bloodjournal78138 ◽

1991 ◽

Vol 78 (1) ◽

pp. 38-43

Author(s):

P von Wussow ◽

H Pralle ◽

HK Hochkeppel ◽

D Jakschies ◽

S Sonnen ◽

...

Keyword(s):

Interferon Alpha ◽

Hairy Cell Leukemia ◽

Mononuclear Cells ◽

Hairy Cell ◽

Cell Leukemia ◽

Recombinant Interferon ◽

Homologous Protein ◽

Ifn Alpha ◽

Interferon Alpha Therapy ◽

Alpha Therapy

To explore the relationship between anti-interferon-alpha (anti-IFN- alpha) antibodies and loss of clinical responsiveness to IFN-alpha treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2 years of therapy, 10 patients developed rIFN-alpha- 2a-neutralizing and 15 rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rIFN-alpha-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN- induced Mx-homologous protein in mononuclear cells after a single injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight of the nine resistant rIFN-alpha patients were found to be highly specific for rIFN-alpha-2a. Therefore, these eight patients were switched to natural IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-alpha, achieving durable objective responses similar to those obtained previously with rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha antibody-positive patients can effectively be treated with nIFN-alpha.

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