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A Strong Expression of CD44-6v Correlates With Shorter Survival of
Patients With Acute Myeloid Leukemia
S. Legras,
U. Günthert,
R. Stauder,
F. Curt,
S. Oliferenko,
H.C. Kluin-Nelemans,
J.P. Marie,
S. Proctor,
C. Jasmin, and
F. Smadja-Joffe
From INSERM U268 Hôpital Paul-Brousse, Villejuif, France; Basel
Institute for Immunology, Basel, Switzerland; University Hospital
Innsbruck, Innsbruck, Austria; U168 Villejuif, France; Leiden
University Medical Center, Leiden, The Netherlands; Hôpital
Hôtel-Dieu, Paris, France; and The Royal Victoria Infirmary,
Newcastle upon Tyne, UK.
CD44 is a ubiquitous cell-surface glycoprotein that displays many
variant isoforms (CD44v) generated by alternative splicing of exons 2v
to 10v. The expression of variant isoforms is highly restricted and
correlated with specific processes, such as leukocyte activation and
malignant transformation. We have herein studied CD44v expression in
acute myeloid leukemia (AML) and, for comparison, in normal
myelopoiesis. Protein expression of total CD44 and of CD44-3v, -6v, and
-9v isoforms has been measured using specific monoclonal antibodies and
flow cytometry. The composition of variant exon transcripts has been
analyzed by semi-quantitative reverse transcriptase-polymerase chain
reaction followed by Southern hybridization with exon-specific probes.
Our data show that (1) CD44-6v isoforms are expressed on 12.0% ± 2.5% of normal CD34+ cells; this expression is sharply
upregulated through monopoiesis and, inversely, downregulated during
granulopoiesis. Also, CD44-3v and CD44-9v isoforms are detected on 10%
and 14% of normal monocytes, respectively. (2) Sixty-nine from a total
of 95 AML patients display a variable proportion (range, 5% to 80%)
of CD44-6v+ leukemic cells. (3) A shorter overall
survival characterizes the group of AML patients displaying more than
20% of CD44-6v+ leukemic cells (8 months v 18 months, P < .02). These data suggest, for the first time,
that the protein expression of CD44-6v containing isoforms may serve as
a new prognostic factor in AML.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3401-3413
© 1998 by The American Society of Hematology.
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