Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells
The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells (LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel for classification of acute leukemias shoul...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Цитувати: | Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells / D.F. Gluzman, V.A. Nadgornaya, L.M. Sklyarenko, M.P. Zavelevych, S.V. Koval, L.Yu. Poludnenko, T.S. Ivanovskaya // Experimental Oncology. — 2008. — Т. 30, № 2. — С. 102–105. — Бібліогр.: 25 назв. — англ. |
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Gluzman, D.F. Nadgornaya, V.A. Sklyarenko, L.M. Zavelevych, M.P. Koval, S.V. Poludnenko, L.Yu. Ivanovskaya, T.S. 2018-06-19T20:05:34Z 2018-06-19T20:05:34Z 2008 Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells / D.F. Gluzman, V.A. Nadgornaya, L.M. Sklyarenko, M.P. Zavelevych, S.V. Koval, L.Yu. Poludnenko, T.S. Ivanovskaya // Experimental Oncology. — 2008. — Т. 30, № 2. — С. 102–105. — Бібліогр.: 25 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/139187 The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells (LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel for classification of acute leukemias should be supplemented with several new markers allowing us to identify more precisely the different forms of the leukemias being of the closely related origin, for example AML M6b and AML M7. The common bipotent LSC in AML M7 of low grade and AML M6b may exist analogous to precursor cell common for megakaryocytopoiesis and erythropoiesis. We have also found the similarity between blast cells in pro-B-ALL [t (4;11), 11q23] and AML M5a [t (9;11), 11q23]. Such similarity of immunophenotype and cytogenetic abnormalities in blast cells in pro-B-ALL and AML M5a may be considered as hint explaining the cases of AML M5a as a recurrence of leukemia in children with originally diagnosed pro-B-ALL. Иммунофенотипический профиль стволовых лейкемических клеток (СЛК) интенсивно изучают в ряде лабораторий мира. Результаты данного исследования подтверждают, что стандартная панель для классификации острых лейкозов (ОЛ) должна быть дополнена рядом новых маркеров. Это позволяет более точно идентифицировать близкие по происхождению формы ОЛ, например ОМЛ М6b и ОМЛ М7. Предполагается существование общей низкодифференцированной бипотентной ЛСК при ОМЛ М7 и ОМЛ М6b, подобной нормальной общей клетке-предшественнице мегакариоцитопоэза и эритропоэза. Установлено также сходство бластных клеток при про-В-ОЛЛ с перестройкой хромосомного участка 11q23 и транслокацией (4;11) и бластных клеток при ОМЛ М5а c перестройкой того же хромосомного участка 11q23 и транслокацией (9;11). Подобное сходство иммунофенотипа и цитогенетических аномалий при указанных 2 формах ОЛ объясняет появление бластов с фенотипом ОМЛ М5а при рецидиве заболевания у детей, у которых ранее был диагностирован про-В-ОЛЛ. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Uncategorized Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells Изучение морфоцитохимических и иммунофенотипических признаков стволовых клеток при острых лейкозах Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| spellingShingle |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells Gluzman, D.F. Nadgornaya, V.A. Sklyarenko, L.M. Zavelevych, M.P. Koval, S.V. Poludnenko, L.Yu. Ivanovskaya, T.S. Uncategorized |
| title_short |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| title_full |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| title_fullStr |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| title_full_unstemmed |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| title_sort |
study of morphocytochemical and immunophenotypic features of acute leukemia stem cells |
| author |
Gluzman, D.F. Nadgornaya, V.A. Sklyarenko, L.M. Zavelevych, M.P. Koval, S.V. Poludnenko, L.Yu. Ivanovskaya, T.S. |
| author_facet |
Gluzman, D.F. Nadgornaya, V.A. Sklyarenko, L.M. Zavelevych, M.P. Koval, S.V. Poludnenko, L.Yu. Ivanovskaya, T.S. |
| topic |
Uncategorized |
| topic_facet |
Uncategorized |
| publishDate |
2008 |
| language |
English |
| container_title |
Experimental Oncology |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| format |
Article |
| title_alt |
Изучение морфоцитохимических и иммунофенотипических признаков стволовых клеток при острых лейкозах |
| description |
The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells (LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel for classification of acute leukemias should be supplemented with several new markers allowing us to identify more precisely the different forms of the leukemias being of the closely related origin, for example AML M6b and AML M7. The common bipotent LSC in AML M7 of low grade and AML M6b may exist analogous to precursor cell common for megakaryocytopoiesis and erythropoiesis. We have also found the similarity between blast cells in pro-B-ALL [t (4;11), 11q23] and AML M5a [t (9;11), 11q23]. Such similarity of immunophenotype and cytogenetic abnormalities in blast cells in pro-B-ALL and AML M5a may be considered as hint explaining the cases of AML M5a as a recurrence of leukemia in children with originally diagnosed pro-B-ALL.
Иммунофенотипический профиль стволовых лейкемических клеток (СЛК) интенсивно изучают в ряде лабораторий мира.
Результаты данного исследования подтверждают, что стандартная панель для классификации острых лейкозов (ОЛ) должна
быть дополнена рядом новых маркеров. Это позволяет более точно идентифицировать близкие по происхождению формы
ОЛ, например ОМЛ М6b и ОМЛ М7. Предполагается существование общей низкодифференцированной бипотентной ЛСК
при ОМЛ М7 и ОМЛ М6b, подобной нормальной общей клетке-предшественнице мегакариоцитопоэза и эритропоэза.
Установлено также сходство бластных клеток при про-В-ОЛЛ с перестройкой хромосомного участка 11q23 и транслокацией
(4;11) и бластных клеток при ОМЛ М5а c перестройкой того же хромосомного участка 11q23 и транслокацией (9;11).
Подобное сходство иммунофенотипа и цитогенетических аномалий при указанных 2 формах ОЛ объясняет появление
бластов с фенотипом ОМЛ М5а при рецидиве заболевания у детей, у которых ранее был диагностирован про-В-ОЛЛ.
|
| issn |
1812-9269 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/139187 |
| citation_txt |
Study of morphocytochemical and immunophenotypic features of acute leukemia stem cells / D.F. Gluzman, V.A. Nadgornaya, L.M. Sklyarenko, M.P. Zavelevych, S.V. Koval, L.Yu. Poludnenko, T.S. Ivanovskaya // Experimental Oncology. — 2008. — Т. 30, № 2. — С. 102–105. — Бібліогр.: 25 назв. — англ. |
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2025-11-25T22:54:41Z |
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102 Experimental Oncology 30, 102–105, 2008 (June)
The characterization of leukemic stem cells (LSC)
and their potential differences as compared to normal
hematopoietic stem cells (HSC) are important for un-
derstanding the process of malignant transformation.
The multistage process of hematopoiesis result-
ing in the appearance of the mature cells of the pe-
ripheral blood (erythrocytes, leukocytes, platelets)
is maintained by HSC. The existence of the common
multipotent hematopoietic stem cell (MHSC) is a fun-
damental principle of the modern unipotent scheme of
hematopoiesis [1–3]. MHSCs possess the self-renewal
abilities, high proliferative potential and are capable for
maintaining myelo- and lymphopoiesis.
As early as in 1961, Till and McCulloch [4] elaborated
the technique for cloning the hematopoietic cells in the
spleen of lethally irradiated mouse and gave the first
experimental evidence that HSC in fact exist. Since that
time, the particular progress has been made in defining
the role of factors produced by stromal microenvironment
(cytokines and interleukins) in controlling proliferation and
differentiation of hematopoietic progenitor cells.
The HSC population is a heterogeneous one subdivid-
ing into long-term HSCs (LT-HSCs) and short-term HSCs
(ST-HSCs). While ST-HSCs have limited self-renewal ca-
pacity giving rise to myeloid and lymphoid lineages within
about 8 weeks, LT-HSCs are capable of self-renewal
giving rise to long-term bone marrow culture capable of
differentiating to myeloid and lymphoid lineages. HSC
gives rise to oligolineage-restricted progenitors with
limited ability of self-renewal: the common progenitor
cell of myelopoiesis and the common progenitor cell of
lymphopoiesis. The progenitor cells in turn give rise to
the cells with most limited differentiation potential and
finally to the functionally mature cells.
In the generally recognized scheme of the he-
matopoiesis [2], HSC as well as progenitor cells class
II and III were depicted as the empty circles. Chertkov
and Vorobiov [3] in their scheme of the hematopoiesis
predicted that depending on the phase of cell cycle
HSC and progenitor cells possess the cytomorphologi-
cal features of blasts or lymphocyte-like cells.
Cytomorphological and cytochemical features
of HSC and hematopoietic progenitors. Besides
the analysis of cell population in splenic colonies
develo ped in the lethally irradiated mouse upon graf-
ting the bone marrow cells and the study of the least
differentia ted cells in granulocytic and monocytic-
macrophage colonies and clusters in vitro, another
approach turned out to be promising.
Prof. Butenko in the monograph “Hematopoietic stem
cells and leukemia” published in Ukraine [5] presented
the cytomorphological features of the presumable “can-
didates” for hematopoietic stem cells. In R.E. Kavetsky
Institute of Oncology Problems (Kyiv, Ukraine), the cyto-
logical and cytochemical study of HSC and progenitor
cells has been performed. In particular, the early stages
of the embryonic hematopoie sis in human and mouse
were studied, especially the early hematopoietic cells
in the yolk sac, which later migrate to liver and populate
bone marrow, spleen, thymus, and lymph nodes [6].
Earlier we have demonstrated that the hematopoietic
progenitor cells of classes II–III (according to Chertkov and
Vorobiov’s scheme of hematopoiesis) regarded earlier as
morphologically non-distinguishable turned out to possess
some marker cytochemical features pertinent to more ma-
ture cells of granulocytic lineage (positive peroxidase and
chloracetate esterase activity); monocytic-macrophage
lineage (high non-specific alpha-naphtyl acetate esterase
activity); megakaryocytic lineage (positive acetylcholin es-
terase activity) and T-lymphocyte lineage (granular or dot-
like acid phosphatase reaction) [6]. Our findings together
with the results of several biochemical studies performed in
former USSR may be regarded as the retrospective ratio-
nale substantiating the use of the cytochemical techniques
STUDY OF MORPHOCYTOCHEMICAL AND IMMUNOPHENOTYPIC
FEATURES OF ACUTE LEUKEMIA STEM CELLS
D.F. Gluzman*, V.A. Nadgornaya, L.M. Sklyarenko,
M.P. Zavelevych, S.V. Koval, L.Yu. Poludnenko, T.S. Ivanovskaya
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells
(LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel
for classification of acute leukemias should be supplemented with several new markers allowing us to identify more precisely the
different forms of the leukemias being of the closely related origin, for example AML M6b and AML M7. The common bipotent
LSC in AML M7 of low grade and AML M6b may exist analogous to precursor cell common for megakaryocytopoiesis and eryth-
ropoiesis. We have also found the similarity between blast cells in pro-B-ALL [t (4;11), 11q23] and AML M5a [t (9;11), 11q23].
Such similarity of immunophenotype and cytogenetic abnormalities in blast cells in pro-B-ALL and AML M5a may be considered
as hint explaining the cases of AML M5a as a recurrence of leukemia in children with originally diagnosed pro-B-ALL.
Key Words: leukemic stem cell, acute leukemia, classification, immunophenotype.
Received: February 8, 2008.
*Correspondence: Fax: +380 44 258 1656
E-mail: vals@onconet.kiev.ua
Abbreviatios used: HSC —hematopoietic stem cells; LSC — leu-
kemic stem cells; LT-HSC — long-term HSC; MНSC — multipotent
HSC; ST-HSC — short-term HSC.
Exp Oncol 2008
30, 2, 102–105
Experimental Oncology 30, 102–105, 2008 (June)30, 102–105, 2008 (June) 103
for delineating the various forms and cytological variants
of the acute myeloid and lymphoid leukemias origi nating
from the transformation and the clonal proliferation of
various types of the hematopoietic progenitor cells.
Recently, the immunophenotypic profile of HSC and
hematopoietic progenitor cells has been extensively
studied. In particular, the phenotype of the pluripotent
stem cell is now delineated as CD34+, CD90+, CD172a+,
CD173+, CD174+, CD175+, CD176+, CD224+, CD227+,
CD239+, HLA-DR+. Accordingly, the phenotype of my e -
lo id stem cells is CD33+, CD34+, CD38+, CD117+, CD123+,
CD133+, HLA-DR+, TdT+/–, CD13+/–, CD7+/–, CD230+; the
phenotype of lymphoid stem cells is CD10+, CD34+,
CD38+, CD117+/–, CD124+, CD127+, HLA-DR+, TdT+.
In fact, only identified markers are given in the listed
phenotypes above, and the exact sets of the phenotypic
markers of HSC and hematopoietic progenitor cells in
all lineages are still to be elucidated [7, 11–13].
Leukemic stem cells. Leukemias as well as other
cancers represent the clonal processes. The leukemic
cells infiltrating the bone marrow as well as the leuke-
mic cells detected in the blood and in the organs of the
body are the descendents of the single cell undergo-
ing the malignant transformation (HSC or committed
progenitor cell). There are many functional similari-
ties between the LSC and solid tumor stem cells. The
milestones of the study of HSC and cancer stem cells
are summarized chronologically in Table 1.
The experimental evidence for the existence of
clonogenic or LSC was obtained in 1997 in hete-
rotransplantation experiments in SCID mouse with
severe combined immunodeficiency (lack of В- and
Т-cells) and NOD/SCID (nonobese diabetic x SCID)
mouse (in addition to SCID mouse NK cells are la cking,
the macrophage activity is not detected neither the
complement activation) [12].
Table 1. Milestones of the studies developing the concept of cancer stem cell
1961 Experimental evidence of polypotent
hematopoietic stem cells
Till and McCulloch, 1961 [4]
1967–
1981
Evidence of CML and AML clonality Fialkow et al., 1967;
Fialkow, 1981 [8, 9]
1972–
1973
Elaboration of modern unipotent
scheme of hematopoiesis
Mathe et al., 1972; Chertkov
and Vorobiov, 1973 [2, 3]
1975–
1990
The technology for production of mono-
clonal antibodies against lineage-specific
and differentiation antigens of leukocytes
Kohler, Milstein, 1975 [10]
1988 Use of mouse with severe combined
immunodeficiency (SCID) for study-
ing human hematopoietic cells
Weissman (ref. Passegue
et al., 2003) [11]
1989–
1994
Use of SCID mouse and mouse with
SCID and non-obese diabetes (NOD/
SCID) for studying leukemic cells
Dick et al., 1996 [12]
Passegue et al., 2003 [11]
Huntly, Gilliland, 2005 [13]
1997 Identification of leukemic stem cell Dick et al., 1996 [12]
2003 Identification of stem cell in breast cancer Al-Hajj et al., 2003 [14]
2004 Identification of human brain tumor
initiating cells
Singh et al., 2004 [15]
2005 Prostate cancer stem cells Collins and Maitland, 2005 [16]
2005 Epithelial ovarian cancer stem cells Bapat et al., 2005 [17]
2005 Osteogenic sarcoma stem cells Gibbs et al., 2005 [18]
2005 Melanoma stem cells Fang et al., 2005 [19]
2007 Neuroblastoma stem cells Ross, Spengler, 2007 [20]
2008 Lung cancer stem cells Eramo et al., 2008 [21]
Upon transplantation of leukemic cells from bone
marrow and peripheral blood of AML patients (regard-
less FAB type), most leukemic blasts are not capable to
proliferate. Only a small subset of leukemic cells in the
Table 2. Markers of normal and transformed hematopoietic stem cells and progenitor cells.
Antigen Structure and function Normal expression Expression in hematoblastoses
CD19 Belongs to IgSF family, takes part in signal
transduction controlling B-cell activation
and differentiation
B-cell progenitors; mature B-cells B-cell leukemias and lymphomas
CD34 Sialomucin involved in intercellular adhesion Hematopoietic stem cells and progenitor cells AML and ALL; leukemic stem cells
CD38 ADP-ribosyl cyclase; takes part in the
control of cell activation and proliferation
Progenitor cells of myelopoiesis, T and B cells,
monocytes, activated T and B cells, plasma cells
Non-clonogenic cells in AML, cells in
multiple myeloma
CD45RA Common leukocyte antigen, regulator
of leukocyte activation
В cells, activated T cells, monocytes, macrophages B cell leukemia
CD90 (Thy-1) Participate in differentiation of HSC
and neuronal cells
HSC, Т cells, fibroblasts, stromal cells Blasts in several forms of AML, rare
cases of ALL
CD123 (IL-3Rα) α-subunit of IL-3 receptor Progenitor cells, endothelial cells, stromal cells Blasts in AML; leukemic stem cells
HLA-DR Histocompatibility antigen class II В cells, antigen-presenting cells, progenitor myeloid
cells
Blasts in various forms of AML except
for AML M3, most B cell tumors
CD172a SIRP-1α, belongs to Ig superfamily CD34+ HSC, hemopoietic progenitor cells, monocytes,
macrophages, granulocytes, dendritic cells
–*
CD173 Antigen H (glycotop Fucα1−2Galβ1-4GlcNAcβ),
progenitor of group A and B antigens
Subpopulation of CD34+ HSC, erythrocytes,
platelets, endothelial cells
–*
CD174 Lewis Y antigen Subpopulation of CD34+ HSC, new marker of
hemopoietic progenitor cells, epithelial cells
–*
CD175 Tn antigen (epitope GalNAcα1-, O-linked
with serine or threonine
Subpopulation of HSC, tumors of epithelial origin AML cell lines (HG-1a, HL-60), K-562,
B-cell leukemia (REH, Nalm-6), T-cell
leukemia (Jurkat)
CD176 TF antigen (epitope Gal β1-3GalNAcα1-,
O-linked with serine or threonine
Subpopulation of HSC, different types of cancer cells –*
CD213a1 Low affinity receptor α1 IL-13 Hemopoietic progenitor cells, subpopulation of
peripheral blood leukocytes, B-cells, monocytes,
endothelial cells, fibroblasts
–*
CD224 Ectoenzyme γ-gluta myl transpeptidase HSC, subpopulation of B-cells, CD45RO+ T-cells,
macrophages
–*
CD227 Polymorphic transmembrane epithelial
mucine (MUC-1)
Subpopulation of HSC, B-cells, monocytes, follicular
dendritic cells, glandular and tubular epithelial cells
–*
CD230 PrP-sialoglycoprotein Hemopoietic progenitor cells, lymphocytes,
monocytes, neurons
–*
CD239 B-CAM glycoprotein, belongs to Ig
superfamily
Subpopulation of HSC, erythrocytes, endothelial
cells, basal membrane epithelial cells
–*
*Data on expression of CD172a, CD173, CD174, CD175, CD176, CD213a1, CD224, CD227, CD230, CD239 were not found in available literature.
104 Experimental Oncology 30, 102–105, 2008 (June)
fraction of CD34+CD38– cells was capable of extensive
proliferation (from 0.2 to 1%).
The recent data suggest that the majority of AML
(except for AML M3) as well as CML develop as a result
of mutations accumulated in HSC.
Several markers of normal HSC and progenitor
cells are expressed also in leukemic cells. The data
on the expression, structure, and function of several
antigens expressing on the surface of HSC and pro-
genitor cells as compared with their expression in vari-
ous forms of the malignancies of hematopoietic and
lymphoid tissues are summarized in Table 2.
The immunophenotype of MHSC and LSC in different
leukemias was delineated [11, 12]. In particular, the im-
munophenotype of MHSC in normal hematopoiesis has
been suggested as CD34+CD38–CD90+CD123–CD117+.
The suggested immunophenotype of LSC in acute myelo-
genous leukemia is CD34+CD38–CD90–CD123+CD117–
CD71–HLA-DR–, while in acute lymphoblastic leukemia
the suggested immunophenotype of LSC is CD34+CD38–
Lin–CD10–CD19–. Moreover, in contrast to the normal
HSC, a universal phenotype for LSC may not exist, and
patient-to-patient variations in cell surface antigen ex-
pression may be the rule.
Various cytological forms of acute myeloid leuke-
mia (M0–M7) are believed to originate from a hierarchy
of leukemic stem cell classes that differ in self-renewal
capacities, molecular and cellular features [12].
The results of our studies suggest that the standard
panel for classification of acute leukemias [24] should be
supplemented with several new markers allowing us to
identify more precisely the different forms of leukemias
being of the closely related origin, for example AML M6b
(МPО–, HLA-DR+/–, CD34+, CD117–, CD71+, CD33–/+ and
CD13–/+, CD36+) vs AML M7 (МPО–, HLA-DR+/–, CD34–/+,
CD117–, CD71–/+, CD33+/– or CD13+/–, CD36+/–) (Table 3).
We suggest the existence of the common bipotent LSC in
AML M7 of low grade and AML M6b, which is analogous
to precursor cell common for megakaryocytopoiesis
and erythropoiesis. We have also found the similarity
between the blast cells in pro-B-ALL [МPО-, HLA-DR+,
CD34+ (less than 50% of cells), CD19+ and CD33– (or
their co-expression), t (4;11), 11q23] and AML M5a
[МPО–, HLA-DR+/–, CD34+/–, CD33+ and CD19– (or their
co-expression), t (9;11), 11q23] (Table 4). The similarity
of immunophenotype and cytogenetic abnormalities
in blast cells in pro-B-ALL and AML M5a seems to be
the hint explaining the cases of AML M5a as a recur-
rence of leukemia in children with originally diagnosed
pro-B-ALL. Moreover, the common LSC for pro-B-ALL
and AML M5a further suggest the analogous precursor
cell for the normal hematopoiesis. Therefore, the modern
concept of LSC allows one to analyze in more depth the
mechanisms of leukemic transformation of target cells
in acute leukemias of the closely related origin such as
AML M6 vs AML M7; AML M5a vs pro-B-ALL.
Based on the consistency of CD34+CD38– cell surface
immunophenotype in different AML subtypes except for
M3 and their similarity to the phenotype of normal HSC, a
model of leukemogenesis was proposed [22] suggesting
that the transformation genetic events occur in primitive
stem cells. According to the alternative point of view, that
cells of origin for AML M0–M7 are the lineage committed
hematopoietic progenitors [23, 24]. As was stated by
Weissman [11], the mechanisms of leukemic transforma-
tion involve the increased cell survival, the increased proli-
ferative potential, the increased self-renewal capability, the
genome instability, and the disordered differentiation.
Table 3. Immunophenotype of blasts in AML М6b and AML М7
Acute erythroleukemia (AML М6b) Acute megakaryoblastic leukemia
(AML М7)
МPО– МPО–
HLA-DR+/– HLA-DR+/–
CD34+ CD34–/+
CD117– CD117–
CD71+ CD71+
CD33– and CD13– CD33+/– or CD13+/–
CD36+ CD36+
Table 4. Immunophenotype of blasts in pro-В-ALL and AML М5а
Pro-В-ALL AML М5а
MPO– MPO–
HLA-DR+ HLA-DR+
CD34+ (90–100% cells) CD34+/– (less than 50% cells)
CD19+CD33– (co-expression is
possible)
CD33+CD19– (co-expression is
possible)
t (4;11), 11q23 t (9;11), 11q23
The recent data on the presumptive target cells for
leukemic transformations and the candidates LSC in
various hematopoietic malignancies delineated in ac-
cordance with the recent WHO classification [25] are
summarized in Table 5.
Table 5. Candidate LSC in the tumors of hematopoietic and lymphoid tissues [25]
Chronic myeloproliferative diseases
Chronic myelogenous leukemia Pluripotent bone marrow SC
Chronic eosinophilic leukemia Pluripotent SC in case of t (8;13);
multipotent HSC or committed
eosinophil precursor cell
Polycythemia vera Multipotent HSC
Chronic idiopathic myelofibrosis Multipotent HSC
Essential thrombocytemia Bone marrow SC with variable lineage
potential
Myelodysplastic/myeloproliferative diseases
Chronic myelomonocytic leukemia HSC
Atypical chronic myeloid leukemia Bone marrow myeloid SC
Juvenile myelomonocytic leukemia Multipotent or pluripotent HSC
Myelodysplastic syndromes
Refractory anemia (RA) HSC
Refractory anemia with ringed
sideroblasts (RARS)
HSC
Refractory cytopenia with
multilineage dysplasia (RCMD)
Myeloid SC
Refractory anemia with excess
blast (RAEB)
Myeloid SC
Unclassifiable Myeloid SC
Associated with del (5q)- HSC
Acute myeloid leukemias
AML with recurrent cytogenetic
abnormalities
Myeloid SC with potential to
granulocytic differentiation
AML with 11q23 (MLL) HSC with multilineage potential
AML with multilineage dysplasia HSC
Therapy-related AML HSC
AML not otherwise characterized
AML minimally differentiated and
AML with maturation
Precursor HSC at early stage of
myeloid differentiation
Acute myelomonocytic leukemia HSC with potential to differentiate into
granulocytic and monocytic lineages
Acute monoblastic and monocytic
leukemia
HSC with some commitment to
monocytic differentiation
Acute erythroid leukemia Multipotent HSC with myeloid potential
Acute megakaryoblastic leukemia Precursor cell committed to mega karyo-
cytic and possibly erythroid differentiation
Acute lymphoblastic leukemias
Precursor B-lymphoblastic
leukemia/lymphoma
Precursor B-lymphoblast
Precursor T-lymphoblastic
leukemia/lymphoma
Precursor T-lymphoblast
Experimental Oncology 30, 102–105, 2008 (June)30, 102–105, 2008 (June) 105
CONCLUSION
The identification of LSC in specified types and vari-
ants of the diseases should be an important task in the
routine diagnostic research in leukemia patients. The
identification of LSC and gene expression in heteroge-
neous forms of hemoblastoses differed by cytological,
cytochemical features as well as by immunophenotype
is advantageous for studying in depth molecular and
genetic mechanisms of leukemogenesis. LSC and
not the usual blasts should be regarded as the major
targets for the novel therapeutic modalities.
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ИзученИе морфоцИтохИмИческИх
И ИммунофенотИпИческИх прИзнаков стволовых
клеток прИ острых лейкозах
Иммунофенотипический профиль стволовых лейкемических клеток (СЛК) интенсивно изучают в ряде лабораторий мира.
Результаты данного исследования подтверждают, что стандартная панель для классификации острых лейкозов (ОЛ) должна
быть дополнена рядом новых маркеров. Это позволяет более точно идентифицировать близкие по происхождению формы
ОЛ, например ОМЛ М6b и ОМЛ М7. Предполагается существование общей низкодифференцированной бипотентной ЛСК
при ОМЛ М7 и ОМЛ М6b, подобной нормальной общей клетке-предшественнице мегакариоцитопоэза и эритропоэза.
Установлено также сходство бластных клеток при про-В-ОЛЛ с перестройкой хромосомного участка 11q23 и транслокацией
(4;11) и бластных клеток при ОМЛ М5а c перестройкой того же хромосомного участка 11q23 и транслокацией (9;11).
Подобное сходство иммунофенотипа и цитогенетических аномалий при указанных 2 формах ОЛ объясняет появление
бластов с фенотипом ОМЛ М5а при рецидиве заболевания у детей, у которых ранее был диагностирован про-В-ОЛЛ.
Ключевые слова: стволовая лейкемическая клетка, острые лейкозы, классификация, иммунофенотип.
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