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Paroxysmal nocturnal hemoglobinuria clone in bone marrow of patients with pancytopenia
H Nakakuma1, S Nagakura, N Iwamoto
1Second Department of Internal Medicine, Kumamoto University School of Medicine, College of Medical Science, Japan.
Abstract:
The lack of glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59 on blood cells has a diagnostic value in paroxysmal nocturnal hemoglobinuria (PNH). Because PNH often develops in patients with aplastic anemia (AA), we attempted to detect a PNH clone in the bone marrow (BM) of patients with AA and pancytopenia before affected cells were evident in the peripheral blood (PB). We used flow cytometry with monoclonal antibodies against DAF and CD59 for the detection of the clone. Affected cells were observed in the BM of 3 of 7 patients with AA and 1 of 3 patients with pancytopenia of unknown origin, but not in their PB. All 8 patients with apparent PNH had affected cells in their BM and PB. On the basis of the early appearance of the PNH clone in the BM, a prospective 4-month follow-up study of the PB cells was performed. The study showed the release of affected mature cells first in granulocytes, then in monocytes, and finally in lymphocytes. Ham's test was positive before affected erythrocytes were detected by flow cytometry. Our findings indicate that detection of the PNH clone in BM could be predictive of the development of PNH in patients with AA and pancytopenia.
Insights
Detecting paroxysmal nocturnal hemoglobinuria (PNH) clones in bone marrow (BM) of aplastic anemia (AA) patients can predict PNH development. This early detection in BM precedes peripheral blood findings, aiding in timely diagnosis.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on blood cells.
- Aplastic anemia (AA) is a known precursor to PNH, necessitating early detection methods.
- Diagnostic markers for PNH include the absence of decay-accelerating factor (DAF) and CD59 on blood cells.
Observation:
- Flow cytometry was employed to detect PNH clones using monoclonal antibodies against DAF and CD59.
- PNH clones were identified in the bone marrow (BM) of patients with AA and pancytopenia before appearing in peripheral blood (PB).
- Affected cells were found in BM of 3/7 AA patients and 1/3 pancytopenia patients, but not PB.
Findings:
- All 8 patients with diagnosed PNH showed affected cells in both BM and PB.
- A prospective follow-up revealed the release of PNH-affected cells sequentially: granulocytes, then monocytes, then lymphocytes.
- Ham's test became positive prior to the detection of affected erythrocytes via flow cytometry.
Implications:
- Early detection of PNH clones in BM can predict PNH development in patients with AA and pancytopenia.
- BM analysis offers a predictive marker for PNH, enabling earlier intervention.
- Understanding the cellular release kinetics of PNH clones informs disease progression monitoring.