The immunophenotype of adult t acute lymphoblastic leukemia in Morocco
Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze the immunophenotypic characteristics o...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Цитувати: | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco / A. Lahjouji, F. Bachir, S. Bennani, A. Quessar, S. Amzazi // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 64-69. — Бібліогр.: 41 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859998101114191872 |
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| author | Lahjouji, A. Bachir, F. Bennani, S. Quessar, A. Amzazi, S. |
| author_facet | Lahjouji, A. Bachir, F. Bennani, S. Quessar, A. Amzazi, S. |
| citation_txt | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco / A. Lahjouji, F. Bachir, S. Bennani, A. Quessar, S. Amzazi // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 64-69. — Бібліогр.: 41 назв. — англ. |
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| container_title | Experimental Oncology |
| description | Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features. Patients and Methods: Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were immunophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Results: Proportion of T-ALL among ALL Moroccan patients was 31.0%. Median age of patients was 28 years. Twenty-nine patients were females and 11 were males. 45.0% of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30.0% (12/40) of CD1a+ cortical T-ALL stage and 25.0% (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of progenitor cell markers CD10, CD34 and TdT expression were 14.0; 57.5% and 50.0% respectively. The aberrant expression of B lineage associated antigen CD79a were positive in 20.5% of the cases and the aberrant expression of myeloid antigens CD13 and/or CD33 was found in 22 (55.0%) cases. No significant association was encountered between TdT, CD34 or myeloid antigens positivity and high risk features at presentation as age, sex, and white blood cells. However, myeloid antigens (CD13 and/or CD33) was significantly associated with T-cell maturation stages (p = 0.009). Conclusion: To the best of our knowledge, this is the first report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated antigens expression is frequently associated with immature immunophenotype. Key Words: adult T cell acute lymphoblastic leukemia, immunophenotypic analysis, immunological subtypes, myeloid and T-cell antigens.
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64 Experimental Oncology 37, 64–69, 2015 (March)
THE IMMUNOPHENOTYPE OF ADULT T ACUTE LYMPHOBLASTIC
LEUKEMIA IN MOROCCO
A. Lahjouji1,*, **, F. Bachir1, S. Bennani1, A. Quessar2, S. Amzazi3
1Laboratory of Flow Cytometry, National Institute of Hygiene, Rabat 769, Morocco
2Service of Hematology and Pediatric Oncology, Hospital 20 Août, Casablanca, Morocco
3Mohamed V-Agdal University, Faculty of Sciences, UFR Biochemistry and Immunology, Rabat 769, Morocco
Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries
reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze
the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features.
Patients and Methods: Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were im-
munophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage
phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Results: Proportion
of T-ALL among ALL Moroccan patients was 31.0%. Median age of patients was 28 years. Twenty-nine patients were females
and 11 were males. 45.0% of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30.0% (12/40)
of CD1a+ cortical T-ALL stage and 25.0% (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of pro-
genitor cell markers CD10, CD34 and TdT expression were 14.0; 57.5% and 50.0% respectively. The aberrant expression of B li-
neage associated antigen CD79a were positive in 20.5% of the cases and the aberrant expression of myeloid antigens CD13 and/
or CD33 was found in 22 (55.0%) cases. No significant association was encountered between TdT, CD34 or myeloid antigens
positivity and high risk features at presentation as age, sex, and white blood cells. However, myeloid antigens (CD13 and/or CD33)
was significantly associated with T-cell maturation stages (p = 0.009). Conclusion: To the best of our knowledge, this is the first
report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among
ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated
antigens expression is frequently associated with immature immunophenotype.
Key Words: adult T cell acute lymphoblastic leukemia, immunophenotypic analysis, immunological subtypes, myeloid and T-cell antigens.
Acute lymphoblastic leukemia (ALL) represents
a biologically and clinically heterogeneous group
of diseases characterized by the accumulation of im-
mature lymphoid cells within the bone marrow (BM)
and lymphoid tissues. ALL represents about 80%
of acute leukemias in childhood, where it is the most
frequent malignancy, and accounts for about 20%
of adult acute leukemias [1].
Early classification systems for acute leukemias
were based only on morphological and cytochemical
investigations. Morphology still plays a central role, but
current World Health Organization (WHO) classifi cation
of tumors of hematopoietic and lymphoid tissues incor-
porates also immunophenotyping, cytogenetic and mo-
lecular characteristics that contribute towards defining
bio logically and clinically relevant leukemia subsets [2].
Flow cytometric immunophenotyping of ALL
is fundamental in the modern diagnosis and treatment
of acute leukemia for several reasons. First, the utiliza-
tion of larger panels of monoclonal antibodies to B-cell,
T-cell and myeloid as well as non-lineage-restricted
antigens allows characterization of blast cells by line-
age assignment, evaluation of cell maturation, and
assessment of phenotypic aberrations. Second, immu-
nophenotyping is also essential for recognizing several
subtypes of acute myeloid leukemia (AML) (e.g., mini-
mally differentiated, myeloperoxidase-nega tive AML
and acute megakaryoblastic leukemia) and mixed phe-
notype acute leukemia. Finally, immunophenotyping
is important for monitoring the response to treatment,
including detection of minimal residual disease and
for identifying markers with prognostic implica tion [3].
Malignant lymphoid neoplasms involving the pre-
sence of neoplastic immature lymphoid cells of T-cell
lineage in both the blood and the BM have been
designated as precursor T cell acute lymphoblastic
leukemia (T-ALL)/lymphoblastic lymphoma (T-LBL)
in the recently published WHO classification for he-
matologic neoplasms. When there is extensive involve-
ment in both the BM and the blood, the preferred term
is leukemia. However, if a mass lesion is present with
minimal blood and BM involvement, the appropriate
term is lymphoma [2].
The most important studies about T-ALL/LBL
come from developed countries with regard to their
distribution according to the classical intrathymic
differentiation compartments, clinical features, de-
scription of prognostic factors as well as the outcome.
The purpose of this study is to determine, by flow
cytometry, the frequency and immunophenotypic
features of Moroccan patients with T-ALL. The immu-
nophenotypic findings were correlated to biological
and clinical features in comparison with B-lineage ALL.
Submitted: January 20, 2015.
*Correspondence: Fax: 00212537772067;
E-mail: lahjouji_ali@yahoo.fr
Abbreviations used: ALL — acute lymphoblastic leukemia; AML — acute
myeloid leukemia; BM — bone marrow; ETP — early T-precursor origin;
MPO — myeloperoxidase; PB — peripheral blood; T-ALL — T cell acute
lymphoblastic leukemia; T-LBL — T cell lymphoblastic lymphoma.
**Institution to which the work should be attributed: National Insti-
tute of Hygiene, Rabat 769, Morocco.
Exp Oncol 2015
37, 1, 64–69
Experimental Oncology 37, 64–69, 2015 (March) 65
MATERIALS AND METHODS
Patients. From January 2006 to December 2009,
immunophenotyping was successfully performed
in 130 consecutive adults (≥18 years) newly diagnosed
with ALL (other than L3 subtypes) at the Hematology
and Oncology Hospital, Casablanca, Morocco. Cases
presenting features of a T-lineage phenotype were
subjected to detailed analysis including immuno-
phenotypic, clinical and biological parameters. ALL
diagnosis was performed on May-Grunwald — Gi-
emsa smears. BM or peripheral blood (PB) samples
were collected, prior to treatment, on ethylenediami-
netetraacetic acid (EDTA) tubes. All patients were
con sented to the routine laboratory and hospital
procedures including blood and BM studies. Patients
were analyzed for age, gender, morphological FAB
subtypes, white blood cells (WBC) count, platelets
count and hemoglobin levels, lymphoadenopathy,
splenomegaly, hepatomegaly and cytogenetic data.
Flow cytometry. All EDTA-anticoagulated PB/
BM samples were immediately transported to the Cy-
tometery Laboratory of the National Hygiene Institute
of Morocco for immunophenotyping. All the samples
were evaluated by flow cytometry, using CD45 expres-
sion vs side scatter to analyze the blast cell population
as described earlier [4]. T-lymphoid antigens included
CD1a, CD3, CD4, CD5, CD7 and CD8; B-lymphoid
antigens included CD10, CD19, CD22, and cytoplas-
mic CD79a. Myeloid antigens were myeloperoxidase
(MPO), CD13 and CD33. Precursor-cell antigens
analyzed were CD34, HLA-DR, and TdT. Positive sta-
ining was defined as at least 20% of blast cells sho-
wing expression of the marker of interest. T-lineage
ALL patients were diagnosed based on the positive
expression of CD3 (cytoplasmic and/or surface) and
were classified further into three maturational stages
that were defined as immature T-ALL stage (pro-T and
pre-T ALL): sCD3–, cCD3+, CD7+, CD1a–, CD5+ and/
or CD8+; cortical T-ALL stage: positive for CD1a (ir-
respective of other markers), and medullary T-ALL:
positive for surface CD3 and negative for CD1a (ir-
respective of other markers).
Statistical analysis. The analysis was done using
SPSS 17.0 version. The characteristics of the patients
were compared by the exact χ2 or Fisher tests. All tests
were 2-sided with a p value of less than 0.05 indicating
a statistically significant difference.
RESULTS AND DISCUSSION
Immunophenotypic findings. Of the 130 ALL
cases immunophenotyped, 40 (31.0%) cases were
classified as having T-ALL and 84 (64.5%) cases were
classified as having B-ALL disease. Mixed acute leuke-
mia comprised 6 (4.5%) cases and were dropped from
further evaluation. Table 1 summarizes the frequencies
of antigens expression found in 40 patients diagnosed
with T-ALL in comparison with B-ALL. The cyto-
plasmic CD3 and CD7 were the only surface T-cell
antigens expressed by all cases (100.0%), followed
by CD5 (82.0%), surface CD3 (62.5%), CD4 (34.0%)
and CD8 (31.5%). Co-expression of CD4 and
CD8 was observed in 21.0% of cases whereas lack
of expression of them both was observed in 55.0%
of cases. CD10 was found in 5 cases (14.0%) and
absent in 31 (86.0%) of 36 cases tested for CD10.
CD34 (57.5%), TdT (50%) and HLA-DR positivity
(25.0%) were significantly much lower in T-ALL than
those in B-ALL (77.5; 84.0 and 100.0%, respectively).
The aberrant expression of B-lineage associated an-
tigen CD79a was positive in 20.5% of the cases and
the aberrant expression of myeloid antigens CD13 and/
or CD33 was found in 22 cases (55.0%), more fre-
quently CD13 than CD33. Indeed, CD13 was observed
in 17 (42.5%) patients, whereas CD33 was observed
in 10 (25.0%) cases. Both CD13 and CD33 antigens
were expressed in 5 (12.5%) cases. No difference
was observed in myeloid antigen expression be-
tween T-ALL and B-ALL subgroups (55.0% vs 52.5%,
p = 0.744). According to surface antigens expression
by leukemic cells, 45.0% of patients (18/40) had
features of immature T-ALL phenotype (pro-T and
pre-T ALL), 30.0% (12/40) of cortical T-ALL subtype
and 25.0% (10/40) of medullary T-ALL subtype. Early
T cell precursor-ALL, a very poor prognosis subgroup
defined by its associated distinctive immunopheno-
type (CD1a–, CD8–, CD5 weak with stem-cell/myeloid
markers) [5, 6], was found in 6 (15.0%) cases.
Table 1. Number of patients and frequency (%) cells with individual mar-
ker expression in B-ALL and T-ALL
CD B-ALL (n = 84) T-ALL (n = 40) p
CD1a − 12 (31.5) −
CytCD3 0 (0.0) 40 (100.0) < 0.001
CD3 0 (0.0) 25 (62.5) < 0.001
CD4 − 13 (34.0) −
CD5 − 32 (82.0) −
CD7 3 (3.5) 40 (100.0) < 0.001
CD8 − 12 (31.5) −
CD10 51 (60.5) 5 (14.0) < 0.001
CD13 29 (36.5) 17 (42.5) 0.507
CD19 84 (100.0) 1 (2.5) < 0.001
CD22 84 (100.0) 2 (5.5) < 0.001
CD33 24 (29.0) 10 (25.0) 0.649
CD34 65 (77.5) 23 (57.5) 0.023
CD45 72 (91.0) 36 (97.0) 0.433
CD79a 78 (100.0) 7 (20.5) < 0.001
TdT 68 (84.0) 19 (50.0) < 0.001
HLA-DR 84 (100.0) 10 (25.0) < 0.001
CD4+/CD8+ − 8 (21.0) −
CD4–/CD8– − 21 (55.0) −
CD13+ and/or CD33+ 42 (52.5) 22 (55.0) 0.744
CD13+/ CD33+ 10 (12.5) 5 (12.5) 1.0
Relationship between immunophenotype and
disease characteristics
Clinical characteristics by lineage. Baseline cha-
racteristics of T-ALL patients compared with B-ALL
patients are summarized in Table 2. T-ALL and B-ALL
significantly differed in their presentation. T-cell
disease was more commonly seen in males (72.5%
vs 52.5%, p = 0.033). T-cell disease was more com-
mon in the 18 to 35 years age group (75.0% vs 56.0%,
p = 0.041). There was an association between T-cell
disease and a high WBC with 52.5% of T-ALL pa-
tients having a WBC more than 50 000/μl compared
with 31.0% of B-cell patients (p = 0.021). There
was no statistically significant difference between
groups in terms of splenomegaly and hepatome-
66 Experimental Oncology 37, 64–69, 2015 (March)
galy frequencies whereas lymphadenopathy seems
to be associated with the T-phenotype rather than
with the B-phenotype (84.0% vs 57.0%, p = 0.014).
Cytogenetic data are available for 96 cases including
71 cases of B-ALL and 25 cases for T-ALL. Normal
diploid caryotypes were more frequently in T-lineage
ALL patients than in B-lineage ALL patients (55.0%
vs 29.0%; p = 0.035). The immunophenotype of leu-
kemic blasts from patients with t(9;22) and with t(4;11)
were restricted to B-ALL.
Table 2. Comparison of clinical and biological features of Moroccan adult
patients with B-ALL and T-ALL
Variable
All patients,
n (%)
B-ALL,
n (%)
T-ALL,
n (%) p
124 (100.0) 84 (67.5) 40 (32.5)
Age
Median 31 (18–66) 34 (18–66) 28 (18–66)
≤ 35 77 (62.0) 47 (56.0) 30 (75.0) 0.041
> 35 47 (38.0) 37 (44.0) 10 (25.0)
Sex
male 73 (59.0) 44 (52.5) 29 (72.5) 0.033
female 51 (41.0) 40 (47.5) 11 (27.5)
FAB
ALL L1 11 (9.0) 8 (9.5) 3 (7.5) 0.758
ALL L2 98 (79.0) 67 (79.5) 31 (77.5)
NS 15 (12.0) 9 (11.0) 6 (15.0)
Clinical features*
Lymphadenopathy (%) 69 (63.5) 48 (57.0) 21 (84.0) 0.014
Splenomegaly,
≥ 2 cm (%)
43 (40.0) 32 (39.0) 11 (44.0) 0.657
Hepatomegaly,
≥ 2 cm (%)
27 (27.0) 17 (22.5) 10 (40.0) 0.084
Laboratory data
Leukocyte count 27 325 (510–
513 050)
21 700
(510–
450 000)
50 500
(600–
513 050)
Median (range), /μl
< 50 000/μl 77 (62.0) 58 (69.0) 19 (47.5) 0.021
≥ 50 000/μl 47 (38.0) 26 (31.0) 21 (52.5)
Hemoglobin level* 7.3
(3.0–15.4)
6.9
(3.0–12.8)
9.2
(4.7–15.4)Median (range), g/dl
< 10 g/dl 86 (81.0) 72 (89.0) 14 (56.0) 0.001
≥ 10 g/dl 20 (19.0) 9 (11.0) 11 (44.0)
Platelet count* 32 500
(2000–
570 000)
30 000
(2000–
570 000)
51 000
(10 000–
236 000)
Median (range), /μl
< 100 000/μl 90 (84.0) 71 (86.5) 19 (76.0) 0.220
≥ 100 000/μl 17 (16.0) 11 (13.5) 6 (24.0)
Cytogenetic**
Normal 30 (35.5) 19 (29.0) 11 (55.0) 0.035
Abnormal 55 (65.0) 46 (71.0) 9 (45.0)
Ph 18 (21.0) 18 (27.5) 0 (0.0) 0.008
t(4.11) 4 (4.5) 4 (6.0) 0 (0.0) 0.569
Unsuccessful karyotype 11 (11.5) 6 (8.5) 5 (20.0)
*Complete data are available for 107 cases including 82 cases of B-ALL and
25 cases for T-ALL.
**Cytogenetic data are available for 96 cases including 71 cases of B-ALL
and 25 cases for T-ALL.
NS — not specified; FAB — French-American-British classification; Ph — Phi-
ladelphia chromosome.
Comparison of clinical characteristics in T-cell
maturational stages. The main clinical characteristics
of the 40 patients divided into three immune subtypes
according to the pattern of antigens expression are
summarized in Table 3. As the number of patients
was relatively small and for the purpose of statistic
comparison we arbitrarily defined two groups: imma-
ture group (pro-T and pre-T ALL stages) and mature
group (cortical-T and medullary-T stages). As shown
in Table 3, patients in the mature group had a signifi-
cantly high initial white cell count (more than 50 000/μl)
than those in the immature group (59.0% vs 28.0%,
p = 0.048). In contrast, no significant diffe rence was
observed between the two groups in regard to the oth-
ers initial characteristics such age, sex, platelets, he-
moglobin levels, organ (lymph nodes, liver and spleen)
enlargement and cytogenetic findings.
Table 3. Characteristics of the 40 consecutive patients with T-ALL (n, %)
Variable
Immature
(Pro- and
pre-T)
Cortical-T Medullary-T Mature p
18 (45.0) 12 (30.0) 10 (25.0) 22 (55.0)
Age
Median 28 (18–66) 23 (18–58) 27 (19–49) 28 (18–66)
≤ 35 11 (61.0) 10 (83.5) 9 (90.0) 19 (86.5) 0.140
> 35 7 (39.0) 2 (16.5) 1 (10.0) 3 (13.5)
Sex
male 12 (66.5) 9 (75.0) 8 (80.0) 17 (77.5) 0.455
female 6 (33.5) 3 (25.0) 2 (20.0) 5 (22.5)
FAB
ALL L1 2 (11.0) 0 (0.0) 1 (10.0) 1 (4.5) 0.332
ALL L2 12 (66.5) 11 (92.0) 8 (80.0) 19 (86.5)
NS 4 (22.0) 1 (8.5) 1 (10.0) 2 (9.0)
Clinical fea-
tures*
Lymphadenopa-
thy (%)
6 (75.0) 11 (91.5) 4 (80.0) 15 (88.0) 0.570
Splenomegaly,
≥ 2 cm (%)
3 (30.0) 5 (62.5) 3 (43.0) 8 (53.5) 0.414
Hepatomegaly,
≥ 2 cm (%)
4 (44.5) 4 (40.0) 2 (33.5) 6 (37.5) 1.000
Leukocyte count
Median (range), /μl 21 900
(600–
513 050)
49 800
(1060–
496 000)
125 450
(8880–
253 000)
79 875
(1060–
496 000)
< 50 000/μl 13 (72.0) 6 (50.0) 3 (30.0) 9 (41.0) 0.048
≥ 50 000/μl 5 (28.0) 6 (50.0) 7 (70.0) 13 (59.0)
Hemoglobin level*
Median (range),
g/dl
7.2
(4.7–14.20)
10.0
(5.0–15.40)
10.15
(7.10–12.50)
10.0
(5.0–15.40)
< 10 g/dl 7 (78.0) 4 (40.0) 3 (50.0) 7 (44.0) 0.208
≥ 10 g/dl 2 (22.0) 6 (60.0) 3 (50.0) 9 (56.0)
Platelet count*
Median (range), /μl 70 000
(16 000–
167 000)
50 000
(10 000–
236 000)
50 000
(13 000–
131 000)
50 000
(10 000–
236 000)
< 100 000/μl 5 (62.5) 7 (70.0) 6 (85.5) 13 (76.5) 0.640
≥ 100 000/μl 3 (37.5) 3 (30.0) 1 (14.5) 4 (23.5)
Cytogenetic*
Normal 5 (55.5) 2 (20.0) 3 (50.0) 5 (31.5) 0.458
Abnormal 3 (33.5) 5 (50.0) 2 (33.5) 7 (44.0)
Echec 1 (11.0) 3 (30.0) 1 (16.5) 4 (25.0)
* Complete data are available for 25 cases.
NS — not specified; FAB — French-American-British classification.
p-value indicated that when comparing the immature group and the ma-
ture group. The immature group was consisted of pro-T and pre-T stage,
and the mature group was consisted of cortical-T and medullary-T stage.
Clinical characteristics in relation to TdT, CD34 and
myeloid antigens expression in T ALL. No significant
association was encountered between CD34, TdT
or myeloid antigens positivity and the presenting clinical
and biological features studied (Table 4) apart a statisti-
cal significance association between myeloid antigens
expression and T-cell maturation stages as 63.5%
of the cases expressing myeloid associated markers
were of the immature phenotype compared with 22%
of the myeloid antigens negative cases (p = 0.009).
T-ALL/LBL is an aggressive neoplasm derived from
T-cell progenitors. The disease can initially present
as lymphoblastic lymphoma involving thymus, nodal,
and extranodal sites, and/or as ALL involving prima-
rily PB and BM. This work constitutes the first study
to be carried out in Morocco involving characteriza-
tion of the immunopheno typic profile of cases of adult
Experimental Oncology 37, 64–69, 2015 (March) 67
T-ALL. Our results on the frequency of T-ALL (31%)
subtype was close to the frequency reported by some
authors for France (28.5%) [7] and Italy (26.0%) [8] but
this frequency was higher to the values found in USA
(20.0%) [9] and lower than the percentage reported for
Egypt (50%) [10] and India (53.0%) [11]. The reason for
the differences in the frequency of T-cell immunophe-
notype is unclear. According some publications, T-ALL
is more commonly associated with low socioeconomic
status [12].
When we analyzed the association between clini-
cal and laboratory findings with T-ALL and B-ALL im-
munophenotypic subtypes of ALL, we could confirm
previously published data [13–15] indicating that T-ALL
occurs more frequently in males younger than 35 years
of age and is usually accompanied by a high WBC
count and tumor mass. On the other hand, we con-
firmed that leukemia of the T-cell lineage is commonly
associated with a normal karyotype [16].
Immunophenotyping is essential in the diagnostic
workup of T-ALL/LBL. Lymphoblasts express cytoplas-
mic and/or surface CD3 and other T-lineage makers
(CD1a, CD2, CD4, CD5, CD7 or CD8) as well as one
or more markers of immaturity, including CD1a, CD10,
CD34 and terminal deoxynucleotidyl transferase (TdT).
The latter is a unique intranuclear DNA polymerase that
catalyzes the template-independent addition of de-
oxynucleotides to the 3´-hydroxyl terminus of oligo-
nucleotide primers [17] causing insertion of N regions
during immunoglobulin and T-cell receptor (TCR) gene
rearrangements at the DJ and VDJ junction sites [18,
19]. This mechanism of junctional diversity is essential
to the development of an adult-type immunoglobulin
and TCR repertoire [19]. The presence, frequency,
and clinical significance of TdT in T-ALL have not been
examined extensively. In this study, TdT was expressed
in 50.0% of our patients with T-ALL. This expression
was lower than that detected in recent studies con-
ducted by Zhou et al. [20] and Patel et al. [21] who
detected TdT expression in about 90.0% of T-ALL
cases. The reasons for the differences may be attrib-
uted to different sensitivities of the antibodies as well
as different cut-off levels for the discrimination of posi-
tive and negative cases. Others methodological varia-
tions in detection of TdT expression like fluorochrome
labe ling, varying gates in flow cytometric analysis and
different TdT antibodies recognizing distinct TdT epi-
topes must also be taken in consideration when com-
paring studies on the implications of TdT expression.
On th other hand, TdT negative cases should be carefully
differentiated from mature T-cell neoplasms particularly
in cases that are also negative for HLA-DR and CD34.
Table 4. Presenting clinical and biological features in relation to TdT, CD34 and myeloid antigens (CD13 and/or CD33) expression in the studied adult
T-ALL patients (n, %)
Variable TdT+ TdT− p CD34+ CD34− p MyAg+ MyAg− p
19 (50.0) 19 (50.0) 23 (57.5) 17 (42.5) 22 (55.0) 18 (45.0)
Age
Median 28 (18–66) 27 (18–50) 31 (18–66) 25.5 (18–58) 30 (19–66) 24 (18–49)
≤ 35 14 (73.5) 16 (84.0) 0.693 17 (74.0) 13 (76.5) 1.000 15 (68.0) 15 (83.5) 0.464
> 35 5 (26.5) 3 (16.0) 6 (26.0) 4 (23.5) 7 (32.0) 3 (16.5)
Sex
male 13 (68.5) 14 (73.5) 0.721 16 (69.5) 13 (76.5) 0.730 14 (63.5) 15 (83.5) 0.286
female 6 (31.5) 5 (26.5) 7 (30.5) 4 (23.5) 8 (36.5) 3 (16.5)
FAB
ALL L1 0 (0.0) 3 (16.0) 0.104 1 (4.5) 2 (12.0) 0.595 3 (13.5) 0 (0.0) 0.265
ALL L2 17 (89.5) 12 (63.0) 19 (82.5) 12 (70.5) 16 (72.5) 15 (85.5)
NS 2 (10.5) 4 (21.0) 3 (13.0) 3 (17.5) 3 (13.5) 3 (16.5)
Clinical features*
Lymphadenopathy (%) 10 (100.0) 8 (72.5) 0.214 10 (77.0) 11 (91.5) 0.593 9 (75.0) 12 (92.5) 0.322
Splenomegaly, ≥ 2 cm (%) 7 (50.0) 4 (40.0) 0.697 6 (37.5) 5 (55.5) 0.434 6 (40.0) 5 (50.0) 0.697
Hepatomegaly, ≥ 2 cm (%) 4 (28.5) 6 (60.0) 0.211 5 (31.5) 5 (55.5) 0.397 3 (23.0) 7 (58.5) 0.111
Leukocyte count
Median (range), /μl 25 000
(1060–
205 000)
106 000
(6070–
513 050)
66 000 (600–
513 050)
41 000 (1060–
496 050)
21 900 (600–
513 050)
79 875 (1060–
496 000)
< 50 000/μl 12 (63.0) 9 (47.5) 0.328 11 (48.0) 11 (64.5) 0.289 14 (63.5) 8 (44.5) 0.225
≥ 50 000/μl 7 (37.0) 10 (52.5) 12 (52.0) 6 (35.5) 8 (36.5) 10 (55.5)
Hemoglobin level*
Median (range), g/dl 9.5
(4.7–15.40)
8.85
(7.10–14.20)
7.5
(4.70–14.20)
10.9
(8.00–15.40)
7.6
(4.70–14.20)
10
(5.0–15.40)
< 10 g/dl 8 (53.5) 4 (50.0) 1.000 12 (70.5) 2 (25.0) 0.032 10 (71.5) 4 (36.5) 0.116
≥ 10 g/dl 7 (46.5) 4 (50.0) 5 (29.5) 6 (75.0) 4 (28.5) 7 (63.5)
Platelet count*
Median (range), /μl 52 000
(12 000–
236 000)
35 000
(10 000–
131 000)
52 000
(10 000–
167 000)
50 000
(12 000–
236 000)
52 000
(12 000–
167 000)
50 000
(10 000–
236 000)
< 100 000/μl 10 (77.0) 7 (78.0) 1.000 13 (76.5) 5 (71.5) 1.000 10 (77.0) 8 (73.0) 1.000
≥ 100 000/μl 3 (23.0) 2 (22.0) 4 (23.5) 2 (28.5) 3 (23.0) 3 (27.0)
Cytogenetic*
Normal 7 (46.5) 3 (43.0) 0.896 7 (46.5) 3 (30.0) 0.659 5 (38.5) 5 (42.0) 0.923
Abnormal 5 (33.5) 3 (43.0) 5 (33.5) 5 (50.0) 5 (38.5) 5 (42.0)
Echec 3 (20.0) 1 (14.0) 3 (20.0) 2 (20.0) 3 (23.0) 2 (16.0)
T cell stage*
Immature 6 (31.5) 10 (52.5) 0.189 12 (52.0) 6 (35.5) 0.289 14 (63.5) 4 (22.0) 0.009
Mature 13 (68.5) 9 (47.5) 11 (48.0) 11 (64.5) 8 (36.5) 14 (78.0)
*Complete data are available for 25 cases.
NS — not specified; FAB — French-American-British classification.
68 Experimental Oncology 37, 64–69, 2015 (March)
CD7 was always detected in our T-ALL series.
Although it is one of the most sensitive T-cell marker,
CD7 lacks specificity, as cases of AML or natural killer
cell leukemia can express CD7 too [22]. In the cur-
rent WHO classification system [2], CD3 expression
is considered the only T-cell lineage-specific marker
and is required for T-cell lineage assignment.
CD10 was detected in 14.0% of the T-ALL cases and
CD34 was expressed in 57.5% of cases. The CD10 an-
tigen was originally known as common ALL antigen
(cALLA). It was one of the first markers to identify acute
leukemia in children. In the hematopoietic system,
CD10 regulates stromal dependent B lymphopoiesis.
The majority of B-lineage ALL cases expressed CD10.
However, expression of CD10 has also been reported
in other types of leukemia [23]. CD34 is a human
stage-specific hematopoietic differentiation antigen,
and expressed in early-undifferentiated hematopoietic
stem cells, both in lymphoid and myeloid pathways.
In leukemic cells, it remains expressed over several
stages of lymphoid and myeloid maturation [24, 25].
In our study, the incidence of CD34 expression ap-
peared to be more frequent on B-ALL (77.5%) than
T-ALL (57.5%). This is consistent with previous obser-
vations in both children [26–28] and adult series [22,
29], suggesting a more immature hematopoietic cell
involvement in B-ALL.
According to the stages of normal thymocyte deve-
lopment that they resemble, we stratified our 40 adult
T-ALL cases into three maturational groups. The ma-
jority of cases (45.0%) arise from immature compart-
ment (pro-T and pre-T ALL). This finding is in agree-
ment with previous reports [30, 31]. Two recent studies
have shown that a subset of T-ALL/LBL cases with
an immunophenotype considered being of an early
T-precursor origin (ETP) belongs to a very high risk
group. The ETP immunophenotype is described as lack
of CD1a and CD8, CD5-/weak, and expression of one
or more myeloid or stem cell-related antigens [5, 6].
Both studies focused on pediatric patients and showed
that ETP-positive cases represent 5–13% of T-ALL/LBL
patients. In our study, we found that 6 cases (15.0%)
met the criteria for early T-cell immunophenotype
defined by the following immunoprofile: CD1a–, CD8–,
and CD5+/weak with positivity for myeloid (CD13 and/
or CD33) or stem cell (CD34) antigens.
Malignant blasts often have an abnormal pheno-
type that allows distinction from normal immature
cells. One of these abnormalities is the occurrence
of aberrant phenotypes (or anomalous expression)
which is defined by the co-expression of markers usu-
ally not present on cells of that particular lineage [32].
The frequency of aberrant expression of the B-cell
antigen receptor complex associated protein CD79a
in our T-ALL cases was 20.5% wish was higher than
5.0% recently reported by Patel et al. [21]. The finding
of CD3/CD79a coexpression in ALL raises the question
of whether these CD79a positive cases are genuinely
of T-cell lineage. Pilozzi et al. [33] performed gene
rearrangement studies of the immunoglobulin heavy
chain and TCR gamma genes in a series of CD3+ ALL
with or without CD79a expression detected by im-
munohistochemistry. All of the cases studied showed
TCR gamma gene rearrangement, and none showed
solely immunoglobulin heavy chain gene rearrange-
ment, strongly suggesting that CD3+ cases of ALL are
of T-cell lineage, regardless of CD79a expression.
The incidence of aberrant myeloid antigen expres-
sion in our study is 55.0%, an incidence much higher
than reported previously for adult patients [21, 29,
31] but more close to 51.0% reported by Marks
et al. [34]. Disparities in flow cytometric technolo-
gy immunophenotyping could explain this different
finding. The frequency of myeloid coexpression was
comparable in B and in T-ALL (52.5% vs 55.0%,
p = 0.744). This was different from earlier reports that
My antigen was significantly associated with T cell ALL
cases [35]. The role of myeloid associated antigens
in the prediction of clinical outcome is still controver-
sial. While the few early adult ALL studies had shown
an inferior outcome for My+ ALL patients [36–38] ot-
hers have found similar outcomes [31, 35].
In conclusion, our findings indicate, first: that
the overall immunoprofile of our T-ALL is gene rally
similar to that described in small case series re-
ports [39–41], second: the proportion of T-ALL among
ALL in Morocco is similar to that reported in others
Mediterranean countries like France and Italy. Third,
the expression of myeloid-associated antigens is asso-
ciated with immature immunophenotype of blast cells.
REFERENCES
1. Pui CH, Evans WE. Acute lymphoblastic leukemia.
N Engl J Med 1998; 339: 605–15.
2. WHO classification of tumours of haematopoietic and
lymphoid tissues. S Swerdlow, N Harris, E Jaffe, et al., eds.
IARC: Lyon, 2008.
3. Craig FE, Foon KA. Flow cytometric immunophenoty-
ping for hematologic neoplasms. Blood 2008; 111: 3941–67.
4. Lahjouji A, Bachir F, Bennani S, et al. Clinical impor-
tance of myeloid antigen expression in Moroccan patients with
adult B-lineage acute lymphoblastic leukemia. Neoplasma
2013; 60: 553–60.
5. Inukai T, Kiyokawa N, Campana D, et al. Clinical
significance of early T-cell precursor acute lymphoblastic leu-
kaemia: results of the Tokyo Children’s Cancer Study Group
Study L99–15. Br J Haematol 2012; 156: 358–65.
6. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early
T-cell precursor leukaemia: a subtype of very high-risk acute
lymphoblastic leukaemia. Lancet Oncol 2009; 10: 147–56.
7. Boucheix C, David B, Sebban C, et al. Immunophenotype
of adult acute lymphoblastic leukemia, clinical parameters, and
outcome: an analysis of a prospective trial including 562 tested
patients (LALA87). French Group on Therapy for Adult Acute
Lymphoblastic Leukemia. Blood 1994; 84: 1603–12.
8. Foa R, Baldini L, Cattoretti G, et al. Multimarker phe-
notypic characterization of adult and childhood acute lympho-
blastic leukaemia: an Italian multicentre study. Br J Haematol
1985; 61: 251–9.
9. Ross CW, Stoolman LM, Schnitzer B, et al. Immuno-
phenotypic aberrancy in adult acute lymphoblastic leukemia.
Am J Clin Pathol 1990; 94: 590–9.
Experimental Oncology 37, 64–69, 2015 (March) 69
10. Kamel AM, Assem MM, Jaffe ES, et al. Immuno-
logical phenotypic pattern of acute lymphoblastic leukaemia
in Egypt. Leuk Res 1989; 13: 519–25.
11. Rajalekshmy KR, Abitha AR, Pramila R, et al. Immu-
nophenotyping of acute lymphoblastic leukaemia in Madras,
India. Leuk Res 1994; 18: 183–90.
12. Paes CA, Viana MB, Freire RV, et al. Direct associa-
tion of socio-economic status with T-cell acute lymphoblastic
leukaemia in children. Leuk Res 2003; 27: 789–94.
13. Garand R, Vannier JP, Bene MC, et al. Comparison
of outcome, clinical, laboratory, and immunological features
in 164 children and adults with T-ALL: The Groupe d’Etude
Immunologique des Leucemies. Leukemia 1990; 4: 739–44.
14. Hoelzer D, Gokbuget N. Recent approaches in acute
lymphoblastic leukemia in adults. Crit Rev Oncol Hematol
2000; 36: 49–58.
15. Onciu M, Lai R, Vega F, et al. Precursor T-cell acute
lymphoblastic leukemia in adults: age-related immunopheno-
typic, cytogenetic, and molecular subsets. Am J Clin Pathol
2002; 117: 252–8.
16. Uckun FM, Gajl-Peczalska KJ, Provisor AJ, et al.
Immunophenotype-karyotype associations in human acute
lymphoblastic leukemia. Blood 1989; 73: 271–80.
17. Onciu M, Lorsbach RB, Henry EC, et al. Terminal
deoxynucleotidyl transferase–positive cells in reactive lymph
nodes from children with malignant tumors: incidence,
distribution pattern, and immunophenotype in 26 patients.
Am J Clin Pathol 2002; 118: 248–54.
18. Alt FW, Baltimore D. Joining of immunoglobulin
heavy chain gene segments: implications from a chromosome
with evidence of three D-JH fusions. Proc Natl Acad Sci USA
1982; 79: 4118–22.
19. Cilfillan S, Dierich A, Lemeur M, et al. Mice lacking
TdT: mature animals with an immature lymphocyte repertoire.
Science 1993; 261: 1175–8.
20. Zhou Y, Fan X, Routbort M, et al. Absence of terminal
deoxynucleotidyl transferase expression identifies a subset
of high-risk adult T-lymphoblastic leukemia/lymphoma.
Modern Pathology 2013; 26: 1338–45.
21. Patel JL, Smith LM, Anderson J, et al. The immu-
nophenotype of T-lymphoblastic lymphoma in children and
adolescents: a Children’s Oncology Group report. Br J Hae-
matol 2012; 159: 454–61.
22. Thalhammer-Scherrer R, Mitterbauer G, Simonitsch
I, et al. The immunophenotype of 325 adult acute leuke-
mias: relationship to morphologic and molecular classification
and proposal for a minimal screening program highly predictive
for lineage discrimination. Am J Clin Pathol 2002; 117: 380–9.
23. Faure GC. The GEIL (Groupe d’Etude Immu-
nologique des Leucémies): CD10 in acute leukemias. Hae-
matologica 1997; 82: 205–10.
24. Greaves MF, Brown J, Molgaard HV, et al. Molecular
features of CD34: a hemopoietic progenitor cell-associated
molecule. Leukemia 1992; 6 (Suppl): 131–6.
25. Schmitt C, Eaves CJ, Lansdorp PM. Expression
of CD34 on human B cell precursors. Clin Exp Immunol
1991; 85: 168–73.
26. Tong H, Wang Q, Lu C, et al. Immunophenotypic,
cytogenetic, and clinical features of 207 cases of childhood
acute lymphoblastic leukemia in China. J Pediatr Hematol
Oncol 2011; 33: 437–41.
27. Dakka N, Bellaoui H, Bouzid N, et al. CD10 and
CD34 expression in childhood acute lymphoblastic leukemia
in Morocco: clinical relevance and outcome. Pediatr Hematol
Oncol 2009; 26: 216–31.
28. Bachir F, Bennani S, Lahjouji A, et al. Characteriza-
tion of acute lymphoblastic leukemia subtypes in Moroccan
children. Int J Pediatr 2009; 2009: 674801.
29. Czuczman MS, Dodge RK, Stewart CC, et al. Value
of immunophenotype in intensively treated adult acute lym-
phoblastic leukemia. Cancer and Leukemia Group B Study
8364. Blood 1999; 93: 3931–9.
30. Shimizu H, Handa H, Hatsumi N, et al. Distinctive
disease subgroups according to differentiation stages in adult
patients with T-cell acute lymphoblastic leukemia. Eur J Hae-
matol 2013; 90: 301–7.
31. Vitale A, Guarini A, Ariola C, et al. Adult T-cell acute
lymphoblastic leukemia: biologic profile at presentation and cor-
relation with response to induction treatment in patients enrolled
in the GIMEMA LAL 0496 protocol. Blood 2006; 107: 473–9.
32. Ossenkoppele G, van de Loosdrecht A, Schuurhuis G.
Review of the relevance of aberrant antigen expression by flow cy-
tometry in myeloid neoplasms. Br J Haematol 2011; 153: 421–36.
33. Pilozzi E, Muller-Hermelink HK, Falini B, et al. Gene
rearrangements in T-cell lymphoblastic lymphoma. J Pathol
1999; 188: 267–70.
34. Marks DI, Paietta EM, Moorman AV, et al. T-cell
acute lymphoblastic leukemia in adults: clinical features, im-
munophenotype, cytogenetics, and outcome from the large
randomized prospective trial (UKALL XII/ECOG 2993).
Blood 2009; 114: 5136–45.
35. Vitale A, Guarini A, Ariola C, et al. Absence
of prognostic impact of CD13 and/or CD33 antigen expres-
sion in adult acute lymphoblastic leukemia. Results of the
GIMEMA ALL 0496 trial. Haematologica 2007; 92: 342–8.
36. Hoelzer D, Thiel E, Loffler H, et al. Prognostic factors
in a multicenter study for treatment of acute lymphoblastic
leukemia in adults. Blood 1988; 71: 123–31.
37. Guyotat D, Campos L, Shi ZH, et al. Myeloid surface
antigen expression in adult acute lymphoblastic leukemia.
Leukemia 1990; 4: 664–6.
38. Urbano-Ispizua A, Matutes E, Villamor N, et al. Clini-
cal significance of the presence of myeloid associated antigens
in acute lymphoblastic leukaemia. Br J Haematol 1990; 75: 202–7.
39. Lewis RE, Cruse JM, Sanders CM, et al. The immu-
nophenotype of pre-TALL/LBL revisited. Exp Mol Pathol
2006; 81: 162–5.
40. Uyttebroeck A, Vanhentenrijk V, Hagemeijer A, et al.
Is there a difference in childhood T-cell acute lymphoblastic
leukaemia and T-cell lymphoblastic lymphoma? Leukaemia
Lymphoma 2007; 48: 1745–54.
41. Hoelzer D, Gokbuget N. T-cell lymphoblastic lym-
phoma and T-cell acute lymphoblastic leukemia: a separate
entity? Clin Lymphoma Myeloma 2009; 9: S214–S22.
Copyright © Experimental Oncology, 2015
|
| id | nasplib_isofts_kiev_ua-123456789-145457 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T16:35:03Z |
| publishDate | 2015 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Lahjouji, A. Bachir, F. Bennani, S. Quessar, A. Amzazi, S. 2019-01-22T10:40:35Z 2019-01-22T10:40:35Z 2015 The immunophenotype of adult t acute lymphoblastic leukemia in Morocco / A. Lahjouji, F. Bachir, S. Bennani, A. Quessar, S. Amzazi // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 64-69. — Бібліогр.: 41 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145457 Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features. Patients and Methods: Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were immunophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Results: Proportion of T-ALL among ALL Moroccan patients was 31.0%. Median age of patients was 28 years. Twenty-nine patients were females and 11 were males. 45.0% of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30.0% (12/40) of CD1a+ cortical T-ALL stage and 25.0% (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of progenitor cell markers CD10, CD34 and TdT expression were 14.0; 57.5% and 50.0% respectively. The aberrant expression of B lineage associated antigen CD79a were positive in 20.5% of the cases and the aberrant expression of myeloid antigens CD13 and/or CD33 was found in 22 (55.0%) cases. No significant association was encountered between TdT, CD34 or myeloid antigens positivity and high risk features at presentation as age, sex, and white blood cells. However, myeloid antigens (CD13 and/or CD33) was significantly associated with T-cell maturation stages (p = 0.009). Conclusion: To the best of our knowledge, this is the first report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated antigens expression is frequently associated with immature immunophenotype. Key Words: adult T cell acute lymphoblastic leukemia, immunophenotypic analysis, immunological subtypes, myeloid and T-cell antigens. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions The immunophenotype of adult t acute lymphoblastic leukemia in Morocco Article published earlier |
| spellingShingle | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco Lahjouji, A. Bachir, F. Bennani, S. Quessar, A. Amzazi, S. Original contributions |
| title | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco |
| title_full | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco |
| title_fullStr | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco |
| title_full_unstemmed | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco |
| title_short | The immunophenotype of adult t acute lymphoblastic leukemia in Morocco |
| title_sort | immunophenotype of adult t acute lymphoblastic leukemia in morocco |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145457 |
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