Modulation of responsiveness of chronic myelogenous leukemia granulocyte-macrophage colony-forming cells to growth regulation following in vivo treatment with recombinant γ-interferon

Louis Pelus, S. Vadhan-Raj

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4 Citations (Scopus)

Abstract

A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant γ-interferon (rγ-IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte-macrophage colony-forming cells (CFU-GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA-DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU-GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive-phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU-GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with rγ-IFN can modulate some of the abnormal growth characteristics of CFU-GM observed in CML.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalAmerican Journal of Hematology
Volume28
Issue number1
StatePublished - 1988
Externally publishedYes

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Granulocyte-Macrophage Progenitor Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Granulocytes
Interferons
Histocompatibility Antigens Class II
Macrophages
Bone Marrow Cells
Growth
Prostaglandins E
Major Histocompatibility Complex
Leukocyte Count
Bone Marrow
Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Clinical Trials, Phase I
HLA-DR Antigens
Therapeutics
Chromosome Aberrations
Agar
Siblings

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Modulation of responsiveness of chronic myelogenous leukemia granulocyte-macrophage colony-forming cells to growth regulation following in vivo treatment with recombinant γ-interferon",
abstract = "A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant γ-interferon (rγ-IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte-macrophage colony-forming cells (CFU-GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA-DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU-GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive-phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU-GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with rγ-IFN can modulate some of the abnormal growth characteristics of CFU-GM observed in CML.",
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AU - Vadhan-Raj, S.

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N2 - A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant γ-interferon (rγ-IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte-macrophage colony-forming cells (CFU-GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA-DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU-GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive-phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU-GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with rγ-IFN can modulate some of the abnormal growth characteristics of CFU-GM observed in CML.

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