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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-03-0718.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 711-721
PHAGOCYTES
Glycosphingolipid expression in acute nonlymphocytic leukemia:
common expression of shiga toxin and parvovirus B19 receptors on early
myeloblasts
Laura L. W. Cooling,
De Sheng Zhang,
Stanley J. Naides, and
Theodore A. W. Koerner
From the Department of Pathology, The University of
Michigan, Ann Arbor; Department of Pathology, University of Iowa, Iowa
City; and Departments of Medicine, Microbiology and Immunology, and
Pharmacology, Penn State-Milton S. Hershey Medical Center,
Hershey, PA.
Glycosphingolipids (GSLs) are complex macromolecules on cell
membranes that have been shown to play a role in neutrophil
differentiation, activation, phagocytosis, and adhesion to both
microorganisms and vascular endothelium. Because GSLs are often cryptic
antigens on cell membranes, little is known regarding GSL expression in early myelopoiesis. To study the latter, myeloblasts were collected from patients with acute nonlymphocytic leukemia (ANLL) who required therapeutic leukocytopheresis for hyperleukocytosis. The neutral GSLs
were isolated and identified by high-performance thin-layer chromatography (HPTLC), HPTLC immunostaining, gas chromatography, nuclear magnetic resonance, and fast atom bombardment-mass
spectrometry. Like mature peripheral blood neutrophils, myeloblasts
expressed glucosylceramide, lactosylceramide, and the neolacto-family
GSLs, lactotriaosylceramide and
neolactotetraosylceramide. Unlike neutrophils and chronic
myeloid leukemia, most ANLL samples also expressed the globo-series
GSLs, globotriaosylceramide and globotetraosylceramide. Globo GSL
expression was strongly associated with a myeloblastic (ANLL M0-M2) and
monoblastic phenotype (M5). A weak association was also noted with
expression of either lymphoid (P < .10) or early
hematopoietic markers (terminal deoxynucleotidyl transferase [TdT],
CD34; P < .10). Globo-positive ANLL samples bound both shiga toxin and parvovirus B19 on HPTLC immunostaining. Based on these
findings, we propose that neolacto and globo GSLs are expressed during
early myeloid differentiation. Globotriaosylceramide expression on
myeloblasts, and possibly myeloid stem cells, may have important
implications for the use of shiga toxin as an ex vivo purging agent in
autologous stem cell transplantation. Expression of
globotetraosylceramide, the parvovirus B19 receptor, on myeloblasts may
also explain the association between B19 infection, aplastic anemia,
and chronic neutropenia of childhood.
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[Abstract]
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