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 Previous Article | Table of Contents
Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 832-833
CORRESPONDENCE
AC133 Antigen Expression Is Not Restricted to Acute Myeloid
Leukemia Blasts But Is Also Found on Acute Lymphoid Leukemia Blasts
and on a Subset of CD34+ B-Cell Precursors
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LETTER |
To the Editor:
Human AC133 antigen is a 5-transmembrane molecule that belongs to the
prominin family.1-4 In the hematopoietic system, AC133 expression is restricted to a subset of CD34+
progenitor/stem cells1 and to leukemic blasts from patients with acute myeloid leukemia (AML).2,5-7 Controversy exists whether the AC133 antigen is also expressed on acute lymphoblastic leukemia (ALL) blasts. One group described low levels of AC133 antigen
expression on the blasts of some ALL samples,2 whereas 3 other groups reported the exclusive expression of this molecule on AML
blasts.5-7 Using multiparameter flow cytometry, we analyzed the correlated expression of AC133 antigen and CD34 in 23 AML and 9 ALL
samples from adult patients, as well as on the surface of normal
CD34+ bone marrow cells. Table
1 shows the distribution of AC133 antigen and CD34 on leukemic blasts in correlation to their morphological classification. In line with previous reports, the majority of CD34+ AML samples (15/18 [83%]) coexpressed the AC133
antigen. Four of the 5 tested CD34 AML samples (80%)
were also AC133+. Notably, these samples exclusively
displayed the M4/M5 French-American-British (FAB) subtypes. Four of 10 CD34+AC133+ AML
samples of the M1/M2 subtypes and 1 of 6 of the
M4/M5 subtypes expressed high levels of AC133
antigen (mean log fluorescence intensity between the second and third
decade). In addition, 1 of 4 CD34AC133+ AML
samples were also AC133bright. Representative plots of a
CD34+AC133bright FAB M2 and a
CD34AC133dim FAB M4 sample are
shown in Fig 1. In contrast to other
reports, our data neither confirm that AC133bright cells
are exclusively found in M4/M5 AML
subtypes2 nor that AC133bright blasts resemble
exclusively the most immature FAB types,7 but rather
suggest that high levels of AC133 antigen expression is observed on
myeloid leukemic blasts of all FAB subtypes.
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| Fig 1.
Coexpression of AC133 antigen and CD34 on leukemic
blasts. Representative AML and ALL blasts were stained with
anti-CD34-FITC (horizontal axis) and AC133-PE (vertical axis) and
analyzed on a FACSCalibur flow cytometer. The mean fluorescence
intensity values are derived from the populations gated on
AC133+ cells.
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Table 1 also demonstrates that 3 of 6 C-ALL, 1 of 1 pro-B ALL, and 1 of
2 T-ALL samples were AC133+. These data are in line with
the observations of Miraglia et al,2 who found AC133
antigen expression on 4 of 6 ALL samples, but do not support the
findings of Snell et al,7 who could not detect AC133
antigen expression on any of the 17 tested ALL samples. In contrast to
Miraglia et al,2 we found high levels of AC133 expression
in some B-lymphoid ALL samples (2/7). Figure 1 shows that 1 AC133bright sample was of the C-ALL and 1 was of the pro-B
ALL phenotype. Notably, the AC133bright blasts of the pro-B
ALL sample were heterogeneous with regard to CD34 expression. However,
whether the CD34+AC133bright and the
CD34AC133bright represent populations of
different maturational stages has yet to be determined.
To analyze whether AC133+ B-lymphoid cells exist also among
nonleukemic hematopoietic precursor cells, normal bone marrow cells enriched for CD34+ cells by MACS technology were stained
with anti-CD34-peridine chlorophyll protein (PerCP),
AC133-phycoerythrin (PE), and anti-CD10-fluorescein isothiocyanate
(FITC) or anti-CD19-FITC, respectively, and analyzed on a FACSCalibur
flow cytometer. Figure 2 shows that the
majority of the CD34+CD10+ and
CD34+CD19+ cells (34.8% v 29.4%) are
AC133. However, a minor
CD34+CD10+ and
CD34+CD19+ B-cell precursor population exists
(15.1% v 5.9%) that is also AC133+ and may
represent the normal counterpart of AC133+ ALL cells. Our
data suggest that AC133 antigen is not only expressed on stem cells and
myeloid progenitor cells and their leukemic counterparts,1,2 but also on ALL blasts and normal
CD34+ B-lymphoid precursor cells.
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| Fig 2.
Coexpression of AC133 and CD10 or CD19 on
CD34+ bone marrow cells. Mononuclear bone marrow cells
were enriched for CD34+ cells by MACS and stained with
anti-CD34-PECY5, AC133-PE, and anti-CD10-FITC or anti-CD19-FITC,
respectively. The plots show expression of AC133 antigen versus CD10 or
CD19 on cells gated on CD34+ cells.
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ACKNOWLEDGMENT |
These studies were supported by the Deutsche Forschungsgemeinschaft
(SFB 510, project A1), by a grant from the Federal Ministry of
Education and Research and the Interdisciplinary Clinical Research Center (project II A1), and by a grant from the Deutsche Krebshilfe (W16/94 Br1).
Hans-Jörg Bühring
Martina Seiffert
Anke Marxer
Burkhard Weiß
Christoph Faul
Lothar Kanz
Wolfram Brugger
Department of Medicine
Division of
Hematology and Oncology
University of Tübingen
Tübingen, Germany
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REFERENCES |
1.
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearny J, Buck DW:
AC133, a novel marker for human hematopoietic stem and progenitor cells.
Blood
90:5002, 1997[Abstract/Free Full Text]
2.
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW:
A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning.
Blood
90:5013, 1997[Abstract/Free Full Text]
3.
Corbeil D, Röper K, Weigmann A, Huttner WB:
AC133 hematopoietic stem cell antigen: Human homologue of mouse kidney prominin or distinct member of a novel protein family?
Blood
91:2625, 1998[Free Full Text] (letter)
4.
Miraglia S, Godfrey W, Buck DW:
A response to AC133 hematopoietic stem cell antigen: Human homologue of mouse kidney prominin or distinct member of a novel protein family?
Blood
91:4390, 1998[Free Full Text] (letter)
5.
Horn PA, Tesch H, Staib P, Kube D, Diel V, Voliotis D:
Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells.
Blood
93:1435, 1999[Free Full Text] (letter)
6.
Kratz-Albers K, Zühlsdorf M, Leo R, Berdel WE, Büchner T, Serve H:
Expression of AC133, a novel stem cell marker, on human leukemic blasts lacking CD34 antigen and on a human CD34+ leukemic cell line: MUTZ-2.
Blood
92:4485, 1998[Free Full Text] (letter)
7.
Snell V, Jackson E, Buck D, Andreeff M:
Expression of the AC133 antigen in leukemic and normal progenitors.
Blood
92:119a, 1998 (abstr, suppl 1)
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