Article du mois


Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

Mourad Aribi, Naima Mesli, Nesrine Remla, Badr-Eddine Sari, Abdesselam Taleb, Hadj Touhami, Mohamed-Amine Bekadja, Zahia Zouaoui- Benhadji, Kamel Bouzid, Kaoual Meguenni

Keywords:
Diffuse large B-cell lymphoma, elderly patients, gemcitabine-based therapy, refractory, relapse

Abstract
Context: Support for non-Hodgkin's lymphoma (NHL) with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria.
Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL) in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine) regimen.
Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%]) received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%]) with GPD (gemcitabine, dexamethasone, cisplatine) protocol.
Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively). Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24) and 19.7% (15.9-23.5), respectively, for the GPD regimen and 10.9% (8.2-13.7) and 11.1% (95% CI 8.5-13.7), respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000), event-free survival (2.03, 1.64-2.52; P < 0.001) and progression-free survival (1.86, 1.46-2.37; P < 0.001).
Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine-based therapy protocol represents a more effective and less toxic than that of ESHAP.

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The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio

Mohamed Brahimi, Soufi Osmani, Abdessamad Arabi, Badra Enta-Soltan, Zohra Taghezout, Belkheir Smain Elkahili, Mohamed Amine Bekadja

Keywords:
Estimation of platelet count, blood smear, red cell: platelet ratio

Abstract
Objective: The estimation of platelet count from blood smears is a daily routine laboratory test, which should be systematic each time the automated count is erroneous.
In our laboratory, we estimate the platelet count indirectly by using the automated red blood cell (RBC) and calculating the platelet count on the basis of the red cell: platelet ratio in a stained blood film. In this study, we attempted to verify the reliability of this technique.
Material and Methods: One hundred ninety-one platelet counts were executed by two laboratory methods: an automated count using an impedance cell counter and then a manual method by reviewing microscopic blood smears.
The number of platelets per 1000 erythrocytes was multiplied by the automated RBC (x106 cells/μl) to give an approximate manual count (x103 cells/μl). Two paired t-test was used for comparison of the two methods.
Results: The regression analyses for the entire data set collected in our study with the two laboratory methods gave the following least squares equation by comparing the automated (y) to the manual method (x): y=0.8548x + 12.013 (r=0.908). The paired t-test showed no significant difference between the two methods (p>0.05) and the Intra-class Correlation Coefficient (ICC) was equal to 0.905.
The plot of the differences between the automated and manual values against their means according to Band and Altman design showed that the difference mean was 3.209 with a standard deviation SD=46.331. We noticed that 93% of the differences were within the agreement limits (mean±2SD), and that 77% of the differences were less than 20,000 platelets/μl.
Conclusion: Estimating platelet count on the basis of the red cell: platelet ratio is a reliable technique and it should be proposed as a method of reference. (Turk J Hematol 2009; 26: 21-4)

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Evolution of Marginal Zone Lymphoma Towards Myeloproliferative Disorder: A Case Report

Abdessamad Arabi, M Brahimi, M.A Bekadja, D Saidi, H Touhami

Keywords:
Marginal zone lymphoma, Myeloproliferative disorders, Flow cytometry, Molecular biology, Bone marrow.

Introduction
Lymphoma is a hematologic malignancy characterized by nodal or extranodal malignant infiltration by monoclonal lymphoid cells (B lineage cells in 70% of the cases). Its etiology is not precisely known. Prolonged life expectancy has resulted in increase of the disease incidence. Marginal zone lymphoma is a low-grade small B-cell lymphoma incorporated in the World Health Organization classification.1,2 Low-grade lymphomas usually demonstrate a characteristic natural history with multiple remissions and relapses. Myeloproliferative syndromes (MPS) are characterized by clonal proliferation of one or more hematopoietic progenitor cell lines such as granulocytes, erythrocytes, megakaryocytes, or mastocytes. These syndromes include chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic eosinophilic leukemia( hypereosinophilic syndrome), chronic neutrophilic leukemia, and systemic mastocytosis.3 They are thought to arise from malignant transformation of hematopoietic stem cells.4
Here, we present a case report of a patient followed and treated for marginal zone lymphoma that evolved to a myeloproliferative disorder.

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Diagnostic de leuce´mie mye´loı¨de chronique au de´cours d'un he´matome sple´nique

Diagnostic of CML after a splenic haematoma

Soufi Osmani, Mohamed Brahimi, Abdessamed Arabi, Bedra Enta-Soltan, Mohamed Amine BekadjaMA

EHU 1er novembre service d'Hématologie et de Thérapie Cellulaire, Oran, Algérie soufiosmani@yahoo.fr

M. C. H. âgé de 41 ans, plombier de profession, tabagique chronique et diabétique, consulte pour des douleurs abdominales.

La palpation abdominale retrouve un ballonnement avec une splénomégalie dont le débord splénique est de 8 cm.

L'hémogramme objective une hyperleucocytose importante (GB = 110 000/mm3), une discrète anémie normochrome normocytaire (Hb = 11,4 g/dL) et un taux de plaquettes normal à 239 000/mm3. Le frottis de sang confirme l'hyperleucocytose et objective une myélémie à
42 %. Le diagnostic de leucémie myéloïde chronique (LMC) est posé, sur la présence du transcrit bcr-abl à 49 %. Le bilan d'hémostase est normal ainsi que le taux de ferritine.

Le traitement de la LMC est commencé. Il associe : imatinib 400 mg/j, allopurinol 600 mg/j, antispasmodiques, antalgiques et une hyperhydratation. Après une semaine de traitement, on note une normalisation du taux des GB et augmentation du taux de plaquettes atteignant 1 661 000/mm3, avec la persistance des douleurs abdominales.

L'échographie abdominale objectivait un important hématome splénique sous-capsulaire et intraparenchymateux tandis que le scanner abdominal confirmait une splénomégalie hétérogène et la présence de formations nodulaires médiospléniques (figure 1) avec des troubles de la perfusion parenchymateuse (figure 2). Devant le risque potentiel de rupture de la rate et après avis chirurgical, une splénectomie a été réalisée.

Les suites opératoires ont été simples, les douleurs abdominales ont cédé et le patient a quitté l'hôpital avec un traitement antiagrégant plaquettaire qui s'ajoutait au traitement de la LMC.

Commentaires

L'hématome de la rate est une complication rare au cours de la LMC par rapport à l'infarctus splénique [1, 2], mais il convient d'évoquer ce diagnostic devant une douleur abdominale vive associée à une splénomégalie [3].

Notre observation est assez originale du fait que le diagnostic de LMC a été posé au décours de douleurs abdominales intenses faisant craindre une rupture de la rate plutôt qu'un infarctus splénique fréquemment décrit au cours de la LMC avec importante splénomégalie.

Cette observation réunit quatre facteurs de risque thrombotique : l'hyperleucocytose, l'hyperplaquettose, le diabète et le tabagisme, mais en même temps des troubles de l'hémostase primaire expliquant l'hématome sous-capsulaire et intraparenchymateux.

La splénectomie n'est réalisée que lorsqu'il y a un risque de rupture potentiel.

Chez notre patient, la décision d'effectuer la splénectomie a été prise devant le tableau clinique de douleurs abdominales vives simulant un abdomen chirurgical, la thrombocytose et l'importance de l'hématome splénique.



Figure 1. Formation nodulaire splénique évoquant un hématome.

Figure 2. Troubles de la perfusion parenchymateuse, hypodensité de la rate évocatrice d'un infarctus splénique.

Références

1. Gupta S, Kakar A. Splenic Infarct of Unusual Aetiology. JIACM 2004 ; 5 : 310-4.
2. Kursner A, Martin Sébastien, Bodenmann P. Douleur irradiant dans l'hypochondre gauche. Schweiz Med Forum 2008 ; 7 : 131-2.
3. Olivier Danon. Infarctus splénique révélateur d'une tuberculose abdominale. Clinique & biologique EMC Consulte 2000 ; 24 : 2404.




• SAL/Ciclosporine vs SAL/Ciclosporine + G-CSF dans les aplasies médullaires (Blood 2007 ; 110 :1756-61. Teramura M et al.)
Le traitement des aplasies médullaires repose sur l'immunosuppression, voire sur l'allogreffe médullaire en cas d'échec. La place du G-CSF est discutée. Dans cette étude japonaise, les auteurs ont randomisé une approche standard par sérum antilymphocytaire (SAL) et ciclosporine, à la même association couplée à du G-CSF, chez 101 patients présentant une aplasie médullaire. L'âge médian était de 54 ans (19-75). Le SAL était administré à la dose de 15 mg/kg pendant 5 jours. Dans le bras B, le lenograstim était administré à la dose de 15 µg/kg tous les 2 jours pendant 28 jours, puis une à 2 injections par semaine jusqu'au jour 84. Le taux de réponse hématologique à 6 mois a été de 57% dans le bras A, vs 77% dans le bras avec G-CSF. Par contre, la survie à 5 ans était la même, 88% vs 94%, et il n'a pas été observé de risque de LAM/MDS supérieur dans le bras B. Le taux de rechute était également plus faible dans le bras B : 15% vs 42%. Au total, l'adjonction de G-CSF semble utile dans le traitement immunosuppresseur de l'aplasie médullaire, même si son rôle reste imparfaitement compris.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Show
DetailView&TermToSearch=17526862

• Efficacité de la combinaison clofarabine-cyclophosphamide dans les LA réfractaires (Blood 2007 ;110 : 1762-69. Karp JE et al.)
Le pronostic des LAM stagne désespérément depuis une vingtaine d'années, principalement en raison de l'absence de découverte de nouvelles molécules actives dans cette pathologie. Parmi les rares molécules nouvelles, la clofarabine est l'une des plus intéressantes. Cet analogue des purines s'est avéré efficace dans plusieurs essais de LA réfractaires. Dans cette étude américaine (John Hopkins et MD Anderson), les auteurs ont combiné la clofarabine avec du cyclophosphamide sur des bases pharmacodynamiques et mécanistiques. Cette étude de phase I/II a inclus 18 patients présentant une LA (L ou M) en rechute ou réfractaire. La dose limitante a été rapidement obtenue sous la forme d'aplasies prolongées. Le taux de réponse au dernier palier était de 50%. Les analyses de pharmacodynamie ainsi que le taux de réponse justifient pour les auteurs l'évaluation de cette approche dans de plus grandes séries.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Show
DetailView&TermToSearch=17562873

• Le CD138 (syndecan-1) est une cible thérapeutique potentielle dans le myélome (Blood 2007 ; 110 : 2041-8. Yang Y et al.)
Le CD138 (syndecan-1) est un protéoglycane lié à des chaînes héparane-sulfate exprimé à la surface des plasmocytes, qu'ils soient physiologiques ou malins. Son expression est restreinte au plasmocyte dans le lignage hématopoiétique, ce qui en fait un marqueur d'identification majeur, mais également une cible thérapeutique attractive. Dans ce travail de l'équipe de Little Rock, les auteurs ont testé dans des modèles animaux différentes approches thérapeutiques ciblant le CD138. La première approche a reposé sur l'administration d'héparinase, une enzyme qui dégrade les chaînes héparane sulfate. La seconde approche a consisté à inhiber l'héparanase, impliquée dans la promotion de la progression tumorale. Enfin, les auteurs ont inhibé l'expression du CD138 par siRNA. L'ensemble de ces actions entraîne une inhibition de la pousse tumorale dans le modèle de souris SCID-hu. Ces données supportent l'idée de cibler cette molécule pour le traitement du myélome.

• Bortezomib et dexaméthasone en première ligne de traitement. Un essai américain a porté sur 32 patients (un tiers avec une β2-m supérieure à 4 mg par l) avec 1,3 mg par m² de cet inhibiteur du protéasome pendant au moins 2 cycles, et de la dexaméthasone en plus en cas de non-réponse après 2 cycles ou de non-RC après 4 cycles, et ce pour un total de 6 cycles. Le taux de réponse est de 88% avec un taux de RC de 6% et de «quasi-RC» (CM détectable uniquement en imuno-fixation) de 19%… soit une excellente réponse chez un patient sur 4 ! La réponse est en règle rapide, obtenue dès les 2 premiers cycles et les effets secondaires sont maintenant assez bien connus : neuropathie de grade 2 ou plus dans 31% des cas ; constipation dans 28% ; myalgies dans 28% ; asthénie dans 25%… Point intéressant : les neuropathies de grade 2 ou 3 s’avèrent réversibles une fois sur 2 dans un délai médian de 3 mois. Enfin, ce traitement n’a pas empêché de mobiliser des CSP en nombre suffisant!

Le délai médian de suivi est de moins de 6 mois ne permettant aucune conclusion sur la qualité des réponses obtenues… mais pas mal quand même, non ? Pour mémoire, ces résultats sont comparables à ceux rapportés par JL Harousseau et al. dans un essai mené par l’IFM : 83% de réponse et 17% de RC!

• PAD = PS-341 ou bortezomib + doxorubicine + dexaméthasone en première ligne également avec ce papier anglais rapportant sur 21 patients et après 4 cycles de traitement, 95% de réponse dont 5 RC… soit près de 1 patient sur 5 ! Vingt patients ont eu ensuite un recueil de CSP efficace et 18 ont été autogreffés avec au final et en intention de traitement : 57% de RC ou quasi-RC ; 24% de très bonnes réponses et 14% de réponses partielles… soit un taux de réponse globale de 95% !!! Qui dit mieux?

Manifestement, le bortezomib va rapidement passer en première ligne de traitement du myélome multiple… d’où l’intérêt du nouveau protocole de l’IFM!

- Rédacteur : Bernard Desablens

- Jagannath S, Durie BG, Wolf J et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005 Jun;129(6):776-83.
- Oakervee HE, Popat R, Curry N et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62.


 

 

Haema 2003; 6(1): 97-99
Case report
Association of a deletion 5q- and a translocation t(2;11) in a case
of refractory anaemia
Mohamed Amine Bekadja1, Evelyne Dupuy², Jean-Marc Zini², Yasmina Rahal1, Samira Zouani²,
Fatiha Touhami1, Mohamed Brahimi1, Hadj Touhami1
1Department of Heamatology, Universitary Hospital of Oran, Oran 31000, Algeria, 2Department of Angio-Haematology,
Universitary Hospital Lariboisière, 75000 Paris, France
Abstract. This paper presents a clinical case with myelodysplasia (refractory anaemia) and 5q- syndrome which shows an unusual additional cytogenetic abnormality [deletion 5q- associated with a t(2;11)].
Fourteen cases have been reported until now in the literature and this is the first case described in Algeria. In addition to this case description; an up to date pathogenic approach is discussed in accordance to new molecular knowledge of myelodysplasia biology.
Key words: refractory anemia • 5q- syndrome • translocation (2;11)
* Correspondence: Mohamed Amine Bekadja, MD, 17 rue Benbassal Mahmoud, Cité Protin, Oran 31000, Algeria, Tel.:+213.41412264, Fax:+213.41412222, e-mail: amine.bekadja@caramail.com

INTRODUCTION
The myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal haematopoietic cell disorders having a maturation arrest and resulting in peripheral blood cytopenia. MDS have a common denominator; they end up to an acute myeloblastic leukaemia, which occurs in a quarter to a third of the cases1. Cytogenetic abnormalities are observed in 30 to 50% of MDS cases2, having not only diagnostic but prognostic value as well. They also help to identify the genes implicated in the MDS pathogenesis. In this
particular case, the translocation t(2;11) is a relatively rare event and only fourteen cases have been described in the literature. At the university hospital of Oran among 39 MDS patients3 we have observed a new case with this translocation together with a 5q deletion4.

CASE REPORT
A 56 year-old man, was consulted in May 1996 for fatigue, weakness and mucocutaneous pallor, installed progressively. His medical history included hypertriglyceridaemia only. On admission, clinical examination
revealed a conscientious patient in a good performance statue (PS1), weakness, exertion dyspnoea, and vertigo. There was no thoracic pain, his blood pressure was 120/70 mm Hg, and the pulse rate was 84/
min. There were no lymphadenopathy, splenomegaly or hepatomegaly.
His haematological profile was as follows: WBC 5x109/l, neutrophils 2,8x109/l, lymphocytes 1,3x109/l, haemoglobin 7g/dl, MCV 110fl, platelet 266x109/l.
The bone morrow aspiration showed an hypercellular marrow with a decreased percentage of the erythroid elements, mononuclear micromegakaryocytes, without any blast excess. Serum ferritin was slightly increased. The iron staining of the bone marrow aspirate did not show any ring sideroblasts. Patient’s blood group was A Rh+. The HBV, HCV, HIV serology was negative. Karyotypic analysis revealed the cytogenetic abnormalities (5q-associated to translocation t(2;11)). The diagnosis of MDS (refractory anaemia) was established by the characteristic karyotypic abnormality.
The patient was treated firstly with androgens (Danasole®), then with corticosteroids and red blood cells transfusion, with no effect. Finally we decided to use red blood cells transfusions alone as needed, using
an iron chelator for preventing iron overload (Deferral ®).
DISCUSSION
In MDS the t(2;11) translocation is a rare event; only fourteen cases have been described in the literature.
Talman et al has described 8 patients with this karyotypic abnormality: 5 had refractory anaemia, 1 refractory anaemia with ringed sideroblasts and 2 acute myeloblastic leukaemia5.
The review of the literature showed that 6 cases had an isolated t(2;11) abnormality, while 8 cases had a t(2;11) translocation together with other karyotypic disorders; del(5q-) being the most frequent (6 cases).
We report here another case with the combination of t(2;11) and del(5q-). All described patients with such a karyotypic abnormality belong to refractory anaemia subtype of MDS. The association between t(2;11) and del(5q-), which occurs frequently in MDS and specially in refractory anaemia, may not be an incidental event. In fact, the break-points on the chromosomes 2, 5 and 11 allow the implication of the oncogenes N myc, C fms and of GM-CSF and IL3 genes in the pathogenesis of the disease.
In fact, the GM-CSF and the IL3 are growth stimulating factors of the proliferation and the differentiation of the granulocytic precursors. They also intervene in the recruitment process of the marrow progenitors6,7.
In addition, the proliferation capacity of these progenitors is dependent on specific genes, including c-myc, c-myb and the c-fos oncogenes8-10.
Cytogenetic studies and fluorescence in situ hybridation (FISH) technique have helped in understanding MDS pathogenesis, analysing regions of genome whose molecular biology is implicated in growth and
proliferation of haematopoietic precursors11.

The deleted part of the long arm of chromosome 5, having a variable length, has a great interest, particularly its zone within 5q14 and 5q35 region. However, most of the research teams who studied the deletions
in the 5q- syndrome agree that the most common short deleted region is located in the 5q31 band12-14.
The genes EGR1, IRF1 and a locus (D5S89) were incriminated in the affection, but their implication has not been proved yet. Conversely, a large number of genes controlling many growth factors and/or their
receptors, including GM-CSF, IL5, and IL4 gene as well as the genes of PDGF, IL4, IL5, and M-CSF receptors and the oncogene C-fms were also subtracted.
The deletion of the long arm of the chromosome 5, particularly of 5q31 region, may be associated to the loss of some genes18, because it has been proven that, in some cases, the missing sequence of the cytogenetically deleted chromosome was also missing in the homologous chromosome 519,20. This may explain the cytomorphologic abnormalities and the cellular abortion due to apoptosis in MDS21. Deletions of chromosome 11 long arm are frequent, such as del (11q14) and del (11q23), while translocations involving chromosome 11 are extremely rare in MDS, as only 14 cases have been published22. The majority of cases with the t(2;11) translocation in MDS belong to refractory anaemia subtype and are associated to the loss of the long arm of the chromosome 5. The translocation t(2;11), as a sole cytogenetic event or in combination
with 5q-, has been found in 12 cases of refractory anaemia and only once in acquired idiopathic sideroblastic anaemia and twice in AML which is not part of the MDS. These results suggest that t(2;11) is a characteristic abnormality of refractory anaemia with 5qanomaly23.
However, a study of the genome and eventually the product of this translocation is crucial to elucidate the role of this t(2;11) translocation in the pathogenesis of refractory anaemia.

REFERENCES
1. Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the myelodysplasic syndromes.
Br J Haematol 1982; 51: 189-199.
2. Lai J L, Fenaux P. Cytogénétique des syndromes myélodysplasiques.
Path Biol 1997; 45: 550-555.
3. Bekadja MA, Zouani S, Touhami H. Primary myelodysplatsic
syndromes: A retrospective study of treatment response and prognostic features in 39 patients in the Western Region of Algeria. Leukemia Res 1997; 21: 54 (abstract).
4. Bekadja MA; Tobelem G; Dupuy E et al. Deletion 5q-
Associated with t(2;11) in a patient with refractory anaemia.
Fifth International Symposium on myelodysplastic syndromes Prague, April 22-24, 1999.
5. Talman P, Accard F, Darbon AB. Translocation (2;11) et délétion (5q) dans les myelodysplasies: Association non aléatoire? XIIIème Congrès de la Société Française d’Hématologie, Paris, 1993; Nouv Rev Fr Hematol 1993; 35: 802 (abstract).
6. Morstyn G, Burgess AW. Hemopoietic growth factors:
A review. Cancer Res 1988; 48: 5624-5637.
7. Stanley ER, Bartocci A, Patinkin D et al. Regulation of very primitive multipotent hemopoietic cells by hemopoietin.
Cell 1986; 45: 667-674.
8. Collins SJ. The H1-60 promyelocytic leukaemia cell line: Proliferation, differentiation, and cellular oncogene expression.
Blood 1987; 70: 1233-1244.
9. Evinger-Hodges MJ, Dicke KA, Gutterman JU et al.
Proto-oncogene expression in human normal bone marrow.
Leukemia 1987; 1: 597-602.
10. Bains MA, Pedrazzoli P, Hoy T et al. C-myb protein in cell cycle of differentiating normal, leukemic and preleukemic Cells. Blood 1988; 72: 174a (abstract).
11. Herry A, Berthou C, Leglise MC et al. Apport de la FISH dans l’étude des remaniements acquis des chromosomes 5 et 7. Hematologie 1998; 4: 67-73.
12. Le Beau MM, Espinosa IIIR, Neuman WL et al. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. Proc Natl Acad Sci USA 1991; 90: 5484-5488.
13. Boultwood J, Fidler C, Lewis S et al. molecular mapping of uncharacteristically small 5q deletions in two patients with the 5q- syndrome: delineation of critical region on 5q and identification of a 5q- breakpoint. Genomics 1994; 19: 425-432.
14. Nagarajan L. Molecular analysis of the 5q- chromosome. Leuk Lymphoma 1995; 17: 361-366.
15. Boultwood J, Lewis S, Wainscoat JS. The 5q- syndrome.
Blood 1994; 84: 3253-3260.
16. Matthew P, Tefferi A, Dewald GW et al. The 5q- syndrome: a single-institution study of 43 consecutive patients.
Blood 1993; 4: 1040-1045.
17. Van den Berghe H, Michaux L. 5q-, twenty five years later: synopsis. Cancer Genet Cytogenet 1996; 94: 1-7.
18. Le Beau MM. Chromosomal abnormalities in therapy related myelodysplasia t(2;11) syndromes. “preleukemia”. Symposium, London, March 13, 1989. Leukemia 1989; 3: 834 (abstract).
19. Boultwood J, Rack C, Kelly S et al. Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion. Proc Natl Acad Sci USA 1991; 88: 6176-6180.
20. Nagarajan L, Zavadil J, Claxton D et al. Consistent loss of the D5S89 locus mapping telomeric to the interleukin gene cluster and centromeric to EGR1 in patients with 5q- chromosome. Blood 1994; 83: 199-208.
21. List AF, Garewal HS, Sandberg AA. The myelodysplasic syndromes: Biology and implication for management.
J Clin Oncol 1990; 8: 1424-1441.
22. Feder M, Finan J, Besa E et al. A2p; 11q chromosome translocation in dysmyelopoietic preleukemia. Cancer Genet Cytogenet 1985; 15: 143-150.
23. Lai JL, Fenaux P. Cytogenetics andmyelodysplastic syndrome.
Nouv Rev Fr Hematol 1991; 32: 160-162.


 

 

Haema 2006; 9(5): 649 - 651
ABO gene frequencies in Oran of Algeria:
Heamotypological situation
Mohamed Brahimi1, Mohamed Saadallah2, Fairouz Lecheheb2, Fatima Zohra Fiad2,
Hamid Belkhadem1, Belkheir Smain Elkahili1, Zohra Taghezout1, Djamel Saidi3, Hadj Touhami3,
Mohamed Amine Bekadja3
1Pediatric Anti-Cancer Center, Emir Abdelkader, Méssèrguine, Oran 31000, Algeria, 2Laboratory of genetics and plants development, Department of Biology, University of Oran, Oran 31000, Algeria, 3Department of Heamatology, Universitary
Hospital of Oran, Oran 31000, Algeria
Abstract. ABO blood group system is a useful tool to anthropologists. Gene frequencies of this system were calculated in many regions, which allowed the construction of haemotypologic cartography
of the world. In this paper, we have calculated the ABO genes frequencies then studied their kinetic by comparing them to those of 1986, found in the archives. We have also compared the haemotypology of Oran with other cities of the neighboring countries.
Key words: ABO system • gene frequencies; haemotypology • cartography.

Correspondence: Mohamed Brahimi, MD, 269, Hai Ennakhla, Canastel, 31132 Oran, Algeria.
Tel.:+213.71485739, e-mail: bmw73dz@yahoo.fr

INTRODUCTION
With the generalization of blood grouping, ABO and rhesus blood group systems became the most useful markers for anthropologists in order to study origin of populations and their migration1-4.
Gene frequencies of several blood group systems were calculated in many regions all over the globeso that a synthetic geographical map had been drawn by Piazza and Cavalli-Sforza5, and many theories had been built on the variation of these frequencies6. This study is a contribution to this world cartography.
MATERIAL AND METHODS
ABO phenotypes of 5361 Oranian inhabitants were picked from the register of the Sénia polyclinic during the period (March 2003 to December 2004).
The ABO phenotyping was performed according to the Beth-Vincent Method7 using the following Anti sera: Anti A, Anti B and Anti AB (Sanofi-Pasteur).
The gene frequencies were calculated using the Bernstein formula8, then compared to those of 1986, found in the archives of the biology department (Sénia University of Oran).
Oran population was compared to four other cities of the neighboring countries: Rabat9, Tunis10, Timbuktu11 and Madrid9. Figure1 shows the geographic situation of Oran among these four cities.
RESULTS
The phenotype and the gene frequencies of ABO blood group system in our sample are summarized in Table 1.

They have been compared to those calculated in 1986. The 2 test showed that there was a significant heterogeneity between these two distributions.
Table 2 shows the gene frequencies of the ABO blood group system in Oran in comparison with the four other cities reported in the literature. The2 test showed that there was homogeneity between the three Maghreb populations, but on the other hand a significant heterogeneity
between Madrid’s, Timbuktu’s and Oran’s populations.



Figure 1. A map showing the geographic situation of Oran city
among the others.

DISCUSSION
The comparison between the present genes proportions to those calculated in 1986, show a considerable heterogeneity.
The frequency of the O gene decreased whereas those of the A and B genes increased. However, the O gene remains the most frequent followed by the A gene then the B gene.
A population is assumed to Hardy-Weinberg equilibrium if the gene frequencies remain stable of a generation to the other. But Hardy-Weinberg’s model is only a theoretical concept in which the conditions of application are rarely combined in the human populations6. Oran, economic capital of the western of Algeria, is a cosmopolitan city and constitutes a destination preferred of many families in Algeria. The emigration as well as the rural exodus make that this gene frequencies fluctuates from a generation to another.
Table2 shows that homogeneity exists between Oran’s; Rabat’s and Tunis’s populations, contrarily what it was yielded in the literature a half century before.
Levique (1955) noticed that the B allele was in high quantity in Morocco where it reached up to 0,144 and this frequency decreases in the region of Saoura in Algeria12.
The frequency of the A allele reached its maximum in the region of Tripoli “Libya” (0,2599), whereas its minimum was observed in the Hoggar “Algeria” (0,0539)13.
After the independence of Algeria in 1962, the populations flow between these big cities, and the miscegenation between these populations of the Arab and Islamic

Table 1: Phenotype and gene frequencies in the population of Oran: the frequencies in our sample were compared to those of 1986
found in the archives of the Senia Biology Department.

Maghreb with the same culture homogenized these frequencies.
The North-south comparison shows clearly that the frequency of the B gene decreases from North to South contrary to the A gene. This observation is compatible with many publications6, 9, 12, 13.
The Algerian north constitutes an isolated region: it is limited at the north by the Mediterranean Sea and to the south by the immense “Sahara desert”. This makes the genetic flow more difficult between Timbuktu, Oran and Madrid. Besides of that, the cultural distances make the miscegenation between these populations less obvious.
ACKNOWLEDGMENTS
We thank the staff of the Sénia polyclinic for their help.
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