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Updated: Sep 21, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Characterization of an inhibitor of granulocyte/monocyte colony formation in leukemic chicken plasma
Abstract:
The plasma of chicks with myeloblastic leukemia (induced by avian myeloblastosis virus, AMV) contained an inhibitor which blocked colony formation in vitro by marrow cells. It eluted in the second protein peak obtained by Sephadex G-200 gel filtration and was found in the diafiltrate following defiltration through a UM 10 membrane under acidic conditions. It was not extractable with chloroform, was heat-stable (65 degrees C, 30 min), pronase-sensitive and had a molecular weight less than or equal to 5000 daltons as determined by high performance liquid chromatography. Thus, it appears to be a small, acid-soluble, heat-stable peptide. It had no interferon activity. It was not present or present only at very low levels in normal plasma. Furthermore, it was not elevated in chicks infected only with the nonleukemogenic helper virus of AMV, and was, therefore, associated with leukemia rather than virus-replication. Leukemic myeloblasts, purified by passage in suspension culture, released the inhibitor. It acted directly on the colony-forming cell and inhibited normal cells much more than leukemic cells. In normal marrow, macrophage and granulocyte progenitors were affected. A similar inhibitor in normal plasma inhibited only granulocyte progenitors.
Insights
Chicks with myeloblastic leukemia produce a small, heat-stable peptide inhibitor that blocks normal marrow cell colony formation. This inhibitor is linked to leukemia, not virus replication, and affects normal cells more than leukemic ones.
Area of Science:
- Hematology
- Oncology
- Virology
Background:
- Avian myeloblastosis virus (AMV) induces myeloblastic leukemia in chicks.
- Leukemic plasma contains an inhibitor affecting marrow cell colony formation.
- The inhibitor's role in leukemia pathogenesis requires elucidation.
Purpose of the Study:
- To characterize the inhibitor found in leukemic chick plasma.
- To determine the inhibitor's association with AMV-induced leukemia.
- To investigate the inhibitor's effect on normal and leukemic marrow cells.
Main Methods:
- Sephadex G-200 gel filtration and UM 10 membrane filtration.
- Chormatography, heat stability, pronase sensitivity, and molecular weight determination (HPLC).
- Assays for colony formation in vitro and interferon activity.
Main Results:
- A small (≤5000 Da), acid-soluble, heat-stable peptide inhibitor was identified.
- The inhibitor was present in leukemic plasma but not significantly in normal plasma or with helper virus infection alone.
- Leukemic myeloblasts released the inhibitor, which preferentially inhibited normal marrow progenitors (macrophage and granulocyte) over leukemic cells.
Conclusions:
- The inhibitor is associated with AMV-induced leukemia and is released by leukemic myeloblasts.
- This peptide inhibitor selectively targets normal hematopoietic progenitors, suggesting a role in leukemia progression.
- A similar, but distinct, inhibitor in normal plasma primarily affects granulocyte progenitors.
