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Acidic isoferritins do not suppress differentiation of mouse myeloid leukemic M1 cells
Abstract:
The differentiation of mouse myeloid leukemia line cells (M1) into macrophages or granulocytes has been reported. Resistant M1 cells which did not differentiate even with a high concentration of inducer of differentiation were isolated from M1 cells. The conditioned medium of the resistant M1 cells (RCM) inhibited the induction of differentiation of M1 cells and the formation of macrophage and granulocyte colonies of normal mouse bone marrow cells. Acidic isoferritins known as negative regulators of normal bone marrow cells (CFU-GM) failed to inhibit the induction of differentiation and growth of M1 cells. The RCM treated with anti-acidic isoferritin serum could inhibit the induction of differentiation of M1 cells as did the untreated RCM. The activities, in RCM, inhibiting growth and differentiation of the normal bone marrow cells were partly neutralized by treatment with the antiserum but most of the activities remained. These results suggest that growth and differentiation of the mouse myeloid leukemia M1 cells are not regulated by acidic isoferritins and other inhibitory activities affecting normal bone marrow colony formation, in addition to acidic isoferritins, are released from M1 cells.
Insights
Resistant mouse myeloid leukemia (M1) cells release factors that inhibit differentiation in both M1 cells and normal bone marrow cells. These factors are distinct from acidic isoferritins, suggesting novel regulatory mechanisms in myeloid leukemia.
Area of Science:
- Hematology
- Cell Biology
- Cancer Research
Background:
- Mouse myeloid leukemia (M1) cell differentiation into macrophages or granulocytes is a known process.
- Resistant M1 cell variants that do not differentiate were successfully isolated.
Purpose of the Study:
- To investigate the regulatory mechanisms of M1 cell differentiation.
- To identify factors released by resistant M1 cells that inhibit differentiation.
Main Methods:
- Isolation of M1 cell variants resistant to differentiation induction.
- Preparation and testing of conditioned medium from resistant M1 cells (RCM).
- Assays for M1 cell differentiation and normal mouse bone marrow cell colony formation (CFU-GM).
- Treatment of RCM with anti-acidic isoferritin serum.
Main Results:
- RCM inhibited M1 cell differentiation and normal bone marrow colony formation.
- Acidic isoferritins did not inhibit M1 cell differentiation or growth.
- Anti-acidic isoferritin serum partially neutralized inhibitory activities in RCM, but most activity remained.
Conclusions:
- M1 cell growth and differentiation are not regulated by acidic isoferritins.
- M1 cells release additional inhibitory factors affecting normal bone marrow colony formation beyond acidic isoferritins.