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Hairy cell leukemia: proliferative response to B cell growth factor, its inhibition by recombinant interferons, and expression of interferon receptors

Thesis/Dissertation ·
OSTI ID:6704061

The malignant B lumphocytes of hairy cell leukemia (HCL) patients are relatively unresponsive to the proliferative influences of standard B cell mitogens as determined by failure to incorporate /sup 3/H-thymidine into DNA. Using chromatographically-purified B cell growth factor (BCGF) proliferative stimulation of HCL cells by this factor was demonstrated. Proliferation was time-dependent and was detectable after 4-6 days of culture and increased up to 10 days of culture. This BCGF-mediated proliferation was completely abrogated by addition of 1000 U/ml alpha inteferon (IFN) at culture initiation, while gamma IFN did not reduce LCL cell proliferation. HCL cells demonstrated specific receptors for ..cap alpha../sub 2/ IGN using /sup 125/I-..cap alpha../sub 2/ IGN. Scatchard analysis estimated the number of type I IGN receptors at approximately 350 per cell, with a K/sub d/ of 7.1 x 10/sup -10/ M, indicating a high-affinity binding site for type I IFN on leukemic cells. The number of type I IFN receptors could be reduced or down-regulated by 18 hour incubation with 100 U/ml ..cap alpha.. or ..beta.. IFN. Similar decreases in binding of /sup 125/I-..cap alpha../sub 2/ IFN were found on cells removed from HCL patients 24 hours following their first treatment with IFN. When incubated in fresh medium, cells exposed to IFN in vivo were able to regenerate their IGN receptors, while those treated in vitro showed no increase in binding of /sup 125/I-..cap alpha../sub 2/ IFN after incubation. These data suggest that the in vitro effects of IFN on HCL cells parallel the in vivo effects and indicate that ..gamma..IFN is unlikely to be clinically active against HCL as ..cap alpha../sub 2/ IFN.

Research Organization:
State Univ. of New York, Buffalo (USA)
OSTI ID:
6704061
Country of Publication:
United States
Language:
English

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Related Subjects

550301* -- Cytology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIBODIES
AZINES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CULTURES
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
ELECTRON CAPTURE RADIOISOTOPES
GROWTH
GROWTH FACTORS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
INTERFERON
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LEUKEMIA
LEUKOCYTES
LYMPHOCYTES
LYMPHOKINES
MATERIALS
MITOGENS
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
REACTION KINETICS
RIBOSIDES
SOMATIC CELLS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
UPTAKE