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Circulating Primitive Stem Cells in Paroxysmal Nocturnal
Hemoglobinuria (PNH) Are Predominantly Normal in Phenotype But
Granulocyte Colony-Stimulating Factor Treatment Mobilizes Mainly PNH
Stem Cells
Roderick J. Johnson,
Andy C. Rawstron,
Steve Richards,
Gareth J. Morgan,
Derek R. Norfolk, and
Sheila O'Connor, and Peter Hillmen
From the Haematological Malignancy Diagnostic Service, The General
Infirmary at Leeds, Leeds, UK.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic
anemia resulting from a somatic mutation in a hemopoietic stem cell. In
most cases of hemolytic PNH, the majority of the marrow cells are
derived from the PNH clone. Recent evidence has indicated, however,
that the majority of the most primitive peripheral blood stem cells
(PBSCs) in PNH appear to be of normal phenotype. This has led to
tentative suggestions that normal PBSCs could be collected and used for
autologous transplantation. We have investigated this possibility in
four PNH patients by treating them with granulocyte colony-stimulating
factor (G-CSF) in an attempt to mobilize normal progenitors. The
expression of glycosylphosphatidylinositol (GPI)-linked proteins was
analyzed by flow cytometry on mature neutrophils, late stem cells
(CD34+/CD38+), and primitive stem cells
(CD34+/CD38 ). The phenotyping and stem
cell quantitation was performed in steady-state blood and post-G-CSF
administration. The most primitive PBSCs
(CD34+/CD38) were almost all normal before
G-CSF treatment, even when the patients' neutrophils were mainly PNH.
However, after G-CSF, the cells that were mobilized into the peripheral
blood were of a similar phenotype to the mature neutrophils, ie, mainly
PNH. It is possible that PNH-stem cells are preferentially destroyed by complement in the peripheral blood leaving only normal cells in the
circulation. After G-CSF, the PNH cells in the marrow are released into
the blood. Our findings suggest that it would be difficult to collect
sufficient numbers of normal stem cells for autologous transplantation.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4504-4508
© 1998 by The American Society of Hematology.
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