Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia

Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells.

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Severe deficiency of natural killer activity in the peripheral blood of patients with hairy cell leukemia

Blood ◽

10.1182/blood.v61.6.1132.1132 ◽

1983 ◽

Vol 61 (6) ◽

pp. 1132-1137 ◽

Cited By ~ 80

Author(s):

LP Ruco ◽

A Procopio ◽

V Maccallini ◽

A Calogero ◽

S Uccini ◽

...

Keyword(s):

Natural Killer ◽

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Nk Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Neoplastic Cells ◽

Killer Activity ◽

Effector Cells ◽

Low Levels

Abstract Natural killer (NK) activity against K-562 tumor cells was evaluated in peripheral blood leukocytes (PBL) obtained from untreated patients affected by hairy cell leukemia (HCL). NK activity present in PBL from 10 HCL patients was at least six-fold lower (p less than 0.01) than that present in PBL from 15 healthy donors. Decreased NK activity in HCL PBL was not due to dilution of the NK effector cells by the neoplastic cells; in fact, NK activity of PBL from 4 HCL patients with less than 5% circulating neoplastic cells was still five-fold lower (p less than 0.01) than that present in normal PBL. Partial characterization of the NK defect in HCL patients indicated that: (A) defective cytotoxicity was not dependent on the duration of the assay; (B) HCL PBL added to normal PBL during the assay did not exert suppressor activity; (C) the NK activity of HCL PBL could be potentiated in vitro by interferon; and (D) low levels of NK activity were associated with reduced numbers of circulating monocytes (p less than 0.01) and of large granular lymphocytes (LGL) (p less than 0.01). In conclusion, our results indicate that the low levels of NK activity present in the peripheral blood of HCL patients may be related to reduced numbers of circulating effector cells.

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Discordant effect of interferon on natural killer activity and tumor cell sensitivity to lysis in hairy cell leukemia

Blood ◽

10.1182/blood.v71.4.1141.1141 ◽

1988 ◽

Vol 71 (4) ◽

pp. 1141-1143 ◽

Cited By ~ 11

Author(s):

N Lahat ◽

E Aghai ◽

A Kotler ◽

A Kinarty ◽

E Sobel ◽

...

Keyword(s):

Natural Killer ◽

Tumor Cells ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Blocking Effect ◽

Autologous Tumor ◽

Nk Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Killer Activity

Abstract We studied the action of alpha-interferon (IFN) and interleukin-2 (IL- 2) on natural killer (NK)-rich fractions and autologous tumor cells from two patients with hairy cell leukemia (HCL). The addition of IFN or IL-2 to the NK-rich fractions resulted in a significant increase in NK activity against the autologous tumor cells. This stimulatory effect was blocked if the target hairy cells (HCs) were preincubated with either IFN or IL-2. Pretreatment of the HCs with anti-Tac antibody entirely prevented the blocking effect of IL-2 and partially the blocking effect of IFN. One patient was treated with recombinant alpha c-IFN. After 2 months there was a dramatic reduction in the number of HCs in the peripheral blood coincident with the loss of the protection effect of IFN against NK lysis of the patient's HCs. NK activity against autologous tumor cells correlated poorly with that against the K562 cell line. We conclude that there is a discordant effect of IFN and IL-2 on NK activity and HC sensitivity to lysis. The Tac receptor appears to play a role in this sensitivity. Caution should be exercised in extrapolating the effects of NK activity against K562 cells to those on HC targets.

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Discordant effect of interferon on natural killer activity and tumor cell sensitivity to lysis in hairy cell leukemia

Blood ◽

10.1182/blood.v71.4.1141.bloodjournal7141141 ◽

1988 ◽

Vol 71 (4) ◽

pp. 1141-1143

Author(s):

N Lahat ◽

E Aghai ◽

A Kotler ◽

A Kinarty ◽

E Sobel ◽

...

Keyword(s):

Natural Killer ◽

Tumor Cells ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Blocking Effect ◽

Autologous Tumor ◽

Nk Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Killer Activity

We studied the action of alpha-interferon (IFN) and interleukin-2 (IL- 2) on natural killer (NK)-rich fractions and autologous tumor cells from two patients with hairy cell leukemia (HCL). The addition of IFN or IL-2 to the NK-rich fractions resulted in a significant increase in NK activity against the autologous tumor cells. This stimulatory effect was blocked if the target hairy cells (HCs) were preincubated with either IFN or IL-2. Pretreatment of the HCs with anti-Tac antibody entirely prevented the blocking effect of IL-2 and partially the blocking effect of IFN. One patient was treated with recombinant alpha c-IFN. After 2 months there was a dramatic reduction in the number of HCs in the peripheral blood coincident with the loss of the protection effect of IFN against NK lysis of the patient's HCs. NK activity against autologous tumor cells correlated poorly with that against the K562 cell line. We conclude that there is a discordant effect of IFN and IL-2 on NK activity and HC sensitivity to lysis. The Tac receptor appears to play a role in this sensitivity. Caution should be exercised in extrapolating the effects of NK activity against K562 cells to those on HC targets.

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Hairy cell leukemia: Absence of natural killer activity and of interleukin 1 release in OKM-1+ spleen hairy cells

Clinical Immunology and Immunopathology ◽

10.1016/0090-1229(83)90172-1 ◽

1983 ◽

Vol 26 (1) ◽

pp. 47-55 ◽

Cited By ~ 12

Author(s):

L.P. Ruco ◽

Antonella Stoppacciaro ◽

M. Valtieri ◽

A. Procopio ◽

Stefania Uccini ◽

...

Keyword(s):

Natural Killer ◽

Hairy Cell Leukemia ◽

Interleukin 1 ◽

Natural Killer Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Killer Activity ◽

Hairy Cells

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Rapid restoration of natural killer activity following treatment with 2-chlorodeoxyadenosine in 22 patients with hairy-cell leukemia

European Journal Of Haematology ◽

10.1111/j.1600-0609.1994.tb01279.x ◽

2009 ◽

Vol 52 (1) ◽

pp. 16-20 ◽

Cited By ~ 20

Author(s):

F. Lauria ◽

D. Rondelli ◽

D. Raspadori ◽

D. Benfenati ◽

S. Tura

Keyword(s):

Natural Killer ◽

Hairy Cell Leukemia ◽

Natural Killer Activity ◽

Hairy Cell ◽

Cell Leukemia ◽

Killer Activity ◽

Rapid Restoration

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The diagnosis of hairy cell leukemia can be established by flow cytometric analysis of peripheral blood, even in patients with low levels of circulating malignant cells

American Journal of Hematology ◽

10.1002/ajh.1120 ◽

2001 ◽

Vol 67 (4) ◽

pp. 223-226 ◽

Cited By ~ 21

Author(s):

Dennis B. Cornfield ◽

Debra M. Mitchell Nelson ◽

Lisa M. Rimsza ◽

Danielle Moller-Patti ◽

Raul C. Braylan

Keyword(s):

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Flow Cytometric Analysis ◽

Malignant Cells ◽

Hairy Cell ◽

Cell Leukemia ◽

Flow Cytometric ◽

Low Levels

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Increased 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis in freshly isolated hairy cell leukemia cells

Blood ◽

10.1182/blood.v63.3.690.690 ◽

1984 ◽

Vol 63 (3) ◽

pp. 690-693 ◽

Cited By ~ 8

Author(s):

S Yachnin ◽

V Mannickarottu

Keyword(s):

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Cellular Proliferation ◽

Coenzyme A ◽

Cholesterol Biosynthesis ◽

Clinical Manifestations ◽

Molar Ratio ◽

Hairy Cell ◽

Cell Leukemia ◽

Coenzyme A Reductase

Abstract Freshly isolated hairy cells from the peripheral blood of patients with hairy cell leukemia (HCL) synthesize 3–5-fold greater amounts of cholesterol, lanosterol, and squalene from [1–14C]-acetate than do normal human peripheral blood mononuclear cells under basal conditions of culture (i.e., in the presence of low-density lipoprotein). HCL cells also exhibit an eightfold increase in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. These changes cannot be ascribed to increased rates of cellular proliferation in the HCL cells, nor are they a consequence of an increased rate of loss of newly synthesized cholesterol into the culture medium. The increased rate of cholesterol biosynthesis in HCL cells may result in an increase in their total cellular cholesterol content, as well as in an increase in their plasma membrane cholesterol:phospholipid molar ratio. These changes, in turn, are probably responsible for some of the clinical manifestations of this disease.

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Cell markers in hairy cell leukemia studied in cells from 51 patients

Blood ◽

10.1182/blood.v59.1.52.52 ◽

1982 ◽

Vol 59 (1) ◽

pp. 52-60 ◽

Cited By ~ 71

Author(s):

J Jansen ◽

HR Schuit ◽

CJ Meijer ◽

JA van Nieuwkoop ◽

W Hijmans

Keyword(s):

Heavy Chain ◽

Hairy Cell Leukemia ◽

Lymphocytic Leukemia ◽

Mature Stage ◽

Hairy Cell ◽

Cell Leukemia ◽

Neoplastic Cells ◽

Hairy Cells ◽

Immunoglobulin Levels ◽

Chain Type

Abstract To determine the maturation arrest of the neoplastic cells of hairy- cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM- positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the “switch” phase from the small micro-carrying lymphocyte to the larger Ig- producing lymphocyte or plasma cell.

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Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha [published erratum appears in Blood 1989 Feb;73(2):624]

Blood ◽

10.1182/blood.v72.5.1708.bloodjournal7251708 ◽

1988 ◽

Vol 72 (5) ◽

pp. 1708-1716

Author(s):

SL Giardina ◽

HA Young ◽

CR Faltynek ◽

ES Jaffe ◽

JW Clark ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Cell Receptor ◽

Hairy Cell ◽

Cell Leukemia ◽

Ifn Gamma ◽

Ifn Alpha ◽

Alpha Receptors

We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon- alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor- beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCR beta rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co- existing T-cell clone to account for the TCR beta rearrangement. Although MNCs from this patient bound significantly less IFN-alpha than did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-gamma receptors on our patient's MNCs was four times higher than the number of IFN-alpha receptors and was similar to the number of IFN-alpha receptors on MNCs from HCL patients responsive to IFN-alpha. While various treatments including IFN-alpha, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-gamma were not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCR beta rearranged clone to expand and displace the initially dominant clone.

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