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Expression of nucleolar antigen p145 in bone marrow cells of patients with myeloid leukemias
1Department of Hematological Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Abstract:
The expression of a cell cycle-related nucleolar protein (p145) antigen was examined in the bone marrow aspirates of 45 individuals, three of whom had no malignant disease; 30 had a diagnosis of acute myeloid leukemia (AML), and 12 suffered from chronic myeloid leukemia (CML). While no evidence of p145 expression was found in the three normal bone marrow samples, it was noted to be the highest in patients with active leukemia, be they AML or blastic crisis of CML. There was a direct correlation between the percentage of blasts and the percentage of p145-positive cells in all patients. Double labeling with tritiated thymidine and p145 in AML patients with active leukemia showed that the majority of S-phase cells contained p145. Myeloblasts in both chronic phase and blastic crisis of CML expressed p145. Nine of 12 AML patients studied during remission had less than 5% p145-positive cells, but three showed 11%, 16%, and 33% positive cells. Since functionally/morphologically, these marrows were normal, the appearance of p145 may indicate a proliferative abnormality preceding maturation arrest and development of relapse. Thus we conclude that p145 is more commonly associated with immature cells and may serve as an early indicator of relapse in AML, but requires further study with larger numbers of patients.
Insights
The nucleolar protein p145 is highly expressed in active leukemia (AML, CML) and correlates with blast percentage. Elevated p145 in AML remission may signal early relapse.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Leukemia, specifically Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), involves abnormal proliferation of myeloid cells.
- Identifying reliable biomarkers for disease activity and relapse prediction in leukemia is crucial for patient management.
Purpose of the Study:
- To investigate the expression of a cell cycle-related nucleolar protein, p145, in bone marrow aspirates from patients with AML and CML.
- To determine the correlation of p145 expression with leukemia cell proliferation and disease status (active vs. remission).
Main Methods:
- Bone marrow aspirates from 45 individuals (3 healthy, 30 AML, 12 CML) were analyzed for p145 antigen expression.
- Immunohistochemistry and double labeling with tritiated thymidine were employed to assess p145 expression and cell cycle phase.
Main Results:
- p145 was not detected in normal bone marrow samples.
- Significantly higher p145 expression was observed in patients with active AML and blastic crisis of CML.
- A direct correlation was found between blast percentage and p145-positive cells in leukemia patients.
- The majority of S-phase cells in active AML expressed p145.
- While most AML patients in remission showed low p145 levels (<5%), three exhibited elevated expression (11-33%), despite morphologically normal marrow.
Conclusions:
- p145 is predominantly expressed in immature myeloid cells and is associated with active leukemia.
- Elevated p145 levels in AML patients during remission may indicate an underlying proliferative abnormality and serve as an early indicator of relapse.
- Further studies with larger cohorts are warranted to validate p145 as a predictive biomarker for AML relapse.