Tech Science Daily News

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in Western
countries 1], 2] while it is extremely rare in Africa 10], 11]. In 3 years, only 40 patients with CLL were identified in several centers of Senegal
with an average age of 61 years (Ranges : 48–85 years). This average age is comparable
to Nigerian 10], 11] and Ethiopian 14] studies which found respectively a mean age of 60, 56 and 55 years.

However, this average age at diagnosis is somewhat higher in Western Countries : American
(72 years) 5], English (74 years) 15] or French (72 years) 16]. There is at least 10 years between the age of onset of CLL in African compared to
Westerners. We speculate that Africans present with CLL at a younger age than Western
patients.

These data may support the idea that environmental factors, remaining to be identified,
may be involved. It has been postulated that CLL occurring in younger adults in Africa
is a consequence of recurrent malaria and other infections, resulting in a polyclonal
B-cell proliferation which in an extreme form is hyper reactive malarial splenomegaly
17].

Male dominance has been reported in the most published series 5], 10], 15], 16]. In ours, male dominance was evident with a ratio M/F?=?3.44. A different evolution
according to gender was however raised and proved 3], 18], 19]. Catovsky et al. 4] demonstrates that CLL runs a more benign clinical course in women than in men. Women
were more likely to have Binet stage A than B or C; their overall survival rates at
10 years were better than for men and they had a better overall response to treatment.
No good hypothesis have been advanced to explain the observed trend for a better outcome
in women. However, the implications of gender differences in the pathogenesis of CLL
and its treatment require further studies. Among our 40 cases, 9 were women (4 in
stage A or B and 5 in stage C). We have not however found significant differences
between men and women compared to Binet stages (p?=?0.75).

CD38 is a well-known lymphocyte differentiation antigen with proposed receptor and
adhesion molecule functions. In mature circulating B cells, CD38 ligation induced
proliferation by promoting the expression of CD25, MHC-II, and certain cytokines 20], 21].

The prognosis role of CD38 in CLL was first proposed on the basis of an immunophenotypical
study of CLL cases with known IGHV sequences. CD38 predicted shorter overall survival
rates when expressed on 30 % or more CLL cells 22]. Since this report in 1999, CD38 expression has been well established as an independent
prognostic factor in CLL by numerous reports, but with various cut-off levels. While
Del Poeta et al. 23] and Hamblin et al. 24] proposed 30 % as the best cut-off, others proposed 20 % 25] or even 7 % 26]. Further cooperative studies are still necessary to define a common cut-off level.
We use the cut-off of 30 % in our patients. The CD38 were express in 70 % of patients
from the series; 12 of them were stage A or B and 16 patients in stage C in the Binet
system. We did not find significant difference between the expression of CD38 and
the different stages of Binet (p?=?0.75).

The others evaluated prognostic factors were cytogenetic abnormalities perfomed by
FISH. The 13q deletion was found in 11 patients (44 %), 6 of them were in stage C.
Deletions on the long arm of chromosome 13, specifically involving band 13q14 (del
(13q14)) represent the single most frequently observed cytogenetic aberration in CLL,
occurring in approx. 55 % of all cases 5]. An isolated del 13q14 is typically characterized by a benign course of the disease.
Three of our patients had a biallelic deletion of 13q and they were all in Binet stage
C. Nevertheless it has been demonstrated that, there was no difference in the baseline
characteristics between patients with CLL who had monoallelic or biallelic deletion
of 13q. In addition, there was no significant difference in endpoints, including time
to treatment 27]. Interestingly, it has been shown that the size of the 13q deletion is associated
with outcome, since patients with CLL with larger aberrations have a shorter time
to treatment and overall survival, indicating that several genes included in the deletion
have an effect on the disease course 28], 29].

Trisomy 12 is detected in 11–16 % of patients at diagnosis 9] and is associated with an intermediate prognosis 9], 30], 31]. Seven of our patients had trisomy 12 (28 %) including 4 stage C Binet (p?=?0.74).
The genes involved in the pathogenesis of CLL carrying a trisomy 12 are largely unknown.
Furthermore, the prognostic relevance of trisomy 12 remains a matter of debate 32].

The deletions of 11q22-q23 and 17p13 are known to be associated with poor prognosis
in CLL 5], 9], 31], 32]. The deletion of 11q is most often monoallelic and carried by 10–17 % of patients
with CLL 9], 30]. The minimal deleted region is known to encode several tumor suppressor genes including
ATM which plays an important role in cell cycle regulation. The deletion of 17p is detected
at a frequency of 3–7 % at diagnosis 9], 30]. The 17p deletion often involves the entire p-arm, but some losses are focused to
the 17p13.1 region, which encodes the TP53 gene among several other genes. This gene is a key regulator of the cell cycle. The
11q deletion was found in 2 patients in stage C and 1 B stage while the 3 patients
with 17p deletion were all in stage C. No significance was found between these poor
prognosis deletions and Binet clinical stages (Table 4). This could be explained by the small size of our series as Lai et al. 33] obtained significant differences in the distribution of p53 deletion according to
Binet classification system (P?=?0.008).

The number of lymphocytes count was significantly greater in patients with stage C
than in those in the group with stages A or B (p?=?0.005). A high lymphocytosis could
be associated to poor prognosis in African with CLL. However Shvidel et al. 34] demonstrated that although CLL patients presenting with hyperleukocytosis at diagnosis
generally have an aggressive clinical course, this is not an independent predictor
of survival in CLL. In any case, further studies are needed to better define the role
of lymphocytosis in prognostic factors for CLL.