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Distinct lysozyme content in different subtypes of acute myeloid leukaemic cells: an ultrastructural immunogold study
1Department of Medicine B, Kaplan Hospital, Rehovot, Israel.
Abstract:
Using an ultrastructural immunogold method, we performed a quantitative study on cellular lysozyme (LZ) content in young normal bone marrow cells and in 14 cases of acute myeloid leukaemia (AML) of the M2, M3, M4 and M5 types. In five cases of M2 we found significantly lower LZ content than in normal promyelocytes and than in nine cases of M3, M4 and M5. In M3, M4 and M5 cells a very high LZ content was observed whereas the serum LZ activity was high in M4 and M5 and normal in M3. The intragranular LZ content was especially high in M5 and in most granules of M4 cells. The immunogold reaction (IGR) for LZ was also performed in cells previously reacted for myeloperoxidase (MPO). In M2 the granules showed definite positive MPO reactivity and low LZ density (granulocytic pattern), whereas in M5 we found high granular LZ content and weak or almost negative MPO activity (monocytic pattern). In M4 we found 'granulocytic' and 'monocytic' type of granules in the same cell. The IGR for LZ performed in post-embedded M5 cells which were previously subjected to phagocytosis of latex particles, showed granules that had moved toward the phagosome, releasing LZ without degranulation. The above findings and those showing normal serum LZ in M3 despite their high cellular LZ content, definitely indicate that only leukaemic M4 and M5 cells secrete LZ into their environment, explaining the high serum LZ observed in those leukaemias.
Insights
Acute myeloid leukaemia (AML) subtypes M4 and M5 show high cellular lysozyme (LZ) content and secrete it into the environment, unlike AML M2 and M3. This explains elevated serum LZ levels in M4 and M5 AML.
Area of Science:
- Hematology
- Cell Biology
- Biochemistry
Background:
- Lysozyme (LZ) is an enzyme crucial for immune response.
- Acute myeloid leukaemia (AML) is a heterogeneous group of blood cancers.
- Understanding cellular enzyme content in AML subtypes is vital for diagnosis and treatment.
Purpose of the Study:
- To quantitatively assess cellular lysozyme (LZ) content in normal bone marrow and various AML subtypes (M2, M3, M4, M5).
- To investigate the relationship between cellular LZ, myeloperoxidase (MPO) activity, and serum LZ levels in AML.
- To determine the secretion patterns of LZ from leukaemic cells.
Main Methods:
- Ultrastructural immunogold method for quantitative cellular LZ analysis.
- Immunogold reaction (IGR) for LZ and myeloperoxidase (MPO) in AML cells.
- Observation of LZ release during phagocytosis in M5 AML cells.
Main Results:
- AML M2 subtypes exhibited significantly lower cellular LZ compared to normal cells and M3, M4, M5 subtypes.
- AML M3, M4, and M5 cells showed very high intracellular LZ content.
- AML M4 and M5 cells secreted LZ into their environment, correlating with high serum LZ activity, while M3 cells did not.
Conclusions:
- Leukaemic M4 and M5 cells are the primary source of secreted lysozyme in AML, explaining elevated serum LZ levels.
- Distinct patterns of LZ and MPO expression characterize AML subtypes (e.g., granulocytic in M2, monocytic in M5).
- Cellular LZ content and secretion dynamics vary significantly across AML subtypes, offering potential diagnostic and therapeutic insights.