Inhibitory Effects of Human Leukocyte and Fibroblast Interferons on Normal and Chronic Myelogenous Leukemic Granulocytic Progenitor Cells

Williams, CK; Svet-Moldavskaya, I. A.; Vilček, Ján; Ohnuma, Takao; Jf, Holland

doi:10.1159/000225587

Cited by 84 publications

(1 citation statement)

References 14 publications

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“…They are released as a mixture of glycoproteins upon appropriate stimulation of mammalian cells. One of the biological effects, inhibition of in vitro granulopoiesis, by heterogeneous interferon of human leucocyte origin (IFN-Le) has been repeatedly documented (Greenberg and Mosny, 1977;van't Hull et al, 1978;Teatle et al, 1980;Verma et al, 1979;Williams et al, 1981). In accordance with the in vitro findings, neutropenia has been observed upon in vivo application (Greenberg and Mosny, 1977;Urbaniak et al, 1978;Guttermann et al, 1980).…”

Section: Introductionmentioning

confidence: 86%

The effects of interferon on granulopoiesis in vitro

Müller¹,

Hofmann²,

Cogoli³

et al. 1984

Hematological Oncology

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Colony formation by myeloid progenitor cells (CFU-c) in agar was inhibited to the same extent by heterogeneous human leucocyte IFN (IFN-Le) and 2 different cloned IFN-alpha 2 preparations, but approximately 10 times less by cloned IFN-alpha 1; cluster formation remained unaffected by any of the interferons. An anti-proliferative effect is suggested by both lower cell yield and DNA synthesis in IFN containing liquid cultures. Incubation of cells with IFN for 18 h prior to plating with colony stimulating factor (CSF) reduced colony formation, indicating an altered responsiveness of CFU-c to CSF. In IFN treated cultures no consistent block of morphological differentiation occurred, but granulocyte alkaline phosphatase activity was reduced. Thus, IFN may play a modulatory role on functional markers. Our results indicate that the effects observed with heterogeneous preparations are due to IFN and not to impurities and that various differentiation parameters are unequally affected by IFN.

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Section: Introductionmentioning

confidence: 86%

The effects of interferon on granulopoiesis in vitro

Müller¹,

Hofmann²,

Cogoli³

et al. 1984

Hematological Oncology

View full text Add to dashboard Cite

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Morphological and functional characteristics of short-term and long-term bone marrow cultures in chronic myelogenous leukemia

1999

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Clonogenic capacity of bone marrow progenitors and stromal layers established from bone marrow of 12 patients with CML and 13 healthy controls were evaluated. The initial BFU-E and CFU-GM contents were slightly higher in the CML patients (p > 0.05) in contrast to CFU-GEMM. CFU-GEMM was lower in the patients compared to healthy controls (p < 0.001). In long-term cultures, the number of non-adherent cell population and total clonogenic progenitor cell content decreased gradually in both groups. Weekly evaluation of stromal confluency of adherent cells revealed that establishment of adherent stromal layer was slower in CML patients than in control samples (p < 0.05). At the end of fourth week, the number of samples presenting confluency was 41.7% in the CML group compared with 92.3% in the controls. The initial CD34 positive cell content of the bone marrow samples was similar in both groups. Although CD34 positive cell number in the adherent stromal layer was well preserved in the control group at the end of 4 weeks, this figure decreased significantly in the CML group. The numbers of total adherent cells as well as the total clonogenic progenitor content of adherent layer were also lower in the CML group (3.03% vs 98.2%). When normal CD34+ cells were cultured on IFN-alpha-treated stromal layer followed by the assessment of the long-term culture initiating cells, a reduced capacity to support hemopoietic growth was observed with IFN-alpha-treated normal stroma. This reduction was even higher when CML stroma was treated with IFN-alpha followed by the seeding of the normal CD34+ cells on this stromal layer (26.9% vs 42.8%). These findings show that stromal cells are abnormal in CML patients as well as the progenitor cells, and IFN-alpha treatment causes further defects of the stromal cells.

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Treatment of the blastic phase of chronic myelogenous leukemia with mitoxantrone and high-dose cytosine arabinoside

Kantarjian

Walters

Keating

et al. 1988

Cancer

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Twenty-seven patients in the blastic phase of chronic myelogenous leukemia received combination chemotherapy with mitoxantrone 5 mg/m2 intravenously daily for 5 days, and cytosine arabinoside 3 g/m2 intravenously over 2 hours every 12 hours for six doses. The patients' median age was 42 years (range, 19-61 years), and 26 of them had Philadelphia chromosome-positive disease. Overall, seven patients (26%) achieved complete remission, and one (4%) had a partial remission for an overall response rate of 30%. Eight patients died during remission induction, and 11 had resistant disease. The median survival was 14 weeks for the total population, and 24 weeks for patients achieving a complete remission. The nonmyelosuppressive toxicity of the combination was acceptable; serious neurologic and pulmonary toxicities were uncommon. Significant marrow hypoplasia was observed resulting in a high incidence of febrile episodes (85% of patients). The combination of mitoxantrone and high-dose cytosine arabinoside did not significantly improve overall prognosis. Since chemotherapy continues to produce disappointing results, other innovative approaches need to be explored.

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Inhibitory Effects of Human Leukocyte and Fibroblast Interferons on Normal and Chronic Myelogenous Leukemic Granulocytic Progenitor Cells

Cited by 84 publications

References 14 publications

The effects of interferon on granulopoiesis in vitro

The effects of interferon on granulopoiesis in vitro

Morphological and functional characteristics of short-term and long-term bone marrow cultures in chronic myelogenous leukemia

Treatment of the blastic phase of chronic myelogenous leukemia with mitoxantrone and high-dose cytosine arabinoside

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