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Red cell pyruvate kinase in acute leukemia.
Summary
Red blood cell pyruvate kinase (PK) defects were identified in patients with acute myeloid leukemia. These acquired defects involved reduced PK activity, altered enzyme stability, and changed substrate affinity.
Area of Science:
- Biochemistry
- Hematology
- Oncology
Background:
- Pyruvate kinase (PK) is a critical enzyme in red blood cell glycolysis.
- Defects in PK can lead to hemolytic anemia.
- Understanding PK alterations in leukemia is important for diagnosis and prognosis.
Purpose of the Study:
- To investigate red blood cell pyruvate kinase (PK) activity, kinetics, and stability in patients with acute leukemias.
- To differentiate PK abnormalities between acute myeloid leukemia (AML) and acute non-myeloid leukemia (ANML).
Main Methods:
- Enzyme kinetic tests were performed on red blood cells.
- Assays included PK activity, Michaelis constants (KM) for phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP), and enzyme thermostability.
- Patient cohorts included those with acute myeloid leukemia and acute non-myeloid leukemia.
Main Results:
- An acquired PK defect was observed in patients with acute myeloid leukemia.
- PK enzyme kinetic tests were normal in patients with acute non-myeloid leukemia.
- PK abnormalities manifested as deficient activity (17 patients), decreased thermostability (15 patients), and altered ADP affinity (11 patients).
Conclusions:
- Acquired red blood cell PK deficiency is associated with acute myeloid leukemia.
- PK enzyme analysis can help distinguish AML from ANML.
- These findings highlight the role of PK defects in the pathophysiology of certain leukemias.