[Continuous platelet infusion in patient refractory to platelet transfusion : a retrospective study]. / Transfusion continue de plaquettes chez les patients réfractaires aux transfusions plaquettaires : étude rétrospective.

Platelet transfusion is commonly used for the prevention of bleeding in central thrombocytopenia. It is estimated that 7-34 % of chronically transfused patients become progressively refractory until they no longer have an increase in post-transfusion platelet count. In this case, and in the presence of bleeding, a therapeutic option is continuous transfusion (CT) of platelet concentrates (PC). We performed a retrospective study of patients at the University Hospital of Liege who received a CT between 01/01/2019 and 31/12/2020. We explored the etiology, immune or non-immune, of the refractory state and analyzed the clinical and biological evolution after TC. In our cohort, 13 patients received CT during the study period; for 8 of them, the refractory state was explained by non-immune causes. The mean platelet count increased during CT and in 61 % of cases, an improvement in bleeding symptomatology was obtained.

La transfusion plaquettaire est couramment utilisée pour la prévention des saignements en cas de thrombopénie centrale. On estime que 7 à 34 % des patients transfusés chroniquement deviennent progressivement réfractaires jusqu'à ne plus présenter d'augmentation de la numération plaquettaire post-transfusionnelle. Dans ce cas, et en présence de saignements, une option thérapeutique correspond à la transfusion continue (TC) de concentrés plaquettaires (CP). Nous avons réalisé une étude rétrospective sur les patients du CHU de Liège ayant reçu une TC entre le 01/01/2019 et le 31/12/2020. Nous avons exploré l'étiologie, immune ou non immune, de l'état réfractaire et analysé l'évolution clinique et biologique après TC. Dans notre cohorte, 13 patients ont bénéficié de TC durant la période étudiée; pour 8 d'entre eux, l'état réfractaire s'expliquait par des causes non immunes. La numération plaquettaire moyenne a augmenté durant la TC et, dans 61 % des cas, une amélioration de la symptomatologie hémorragique a été obtenue.

[Evolution of histocompatibility methods in organ transplantation: an update in 2022]. / Évolution des méthodes d'histocompatibilité dans la greffe d'organe : le point en 2022.

The evaluation of anti-HLA immunization in organ transplantation has evolved dramatically since the first lymphocytotoxic crossmatch between donor and recipient was described. The same is true for HLA typing, which can now be performed by high-resolution sequencing. Nevertheless, the transplantation of a totally compatible organ remains an exception and the appearance of anti-HLA antibodies during the transplantation is inevitable, which conditions the long-term survival of the graft. New computer tools are currently being developed to evaluate and quantify the degree of incompatibility between donor and recipient, with a view to predicting the risk of rejection and adapting immunosuppressive therapy in a targeted manner for each patient.

L'évaluation de l'immunisation anti-HLA dans la transplantation d'organe a évolué de façon spectaculaire depuis la description des premiers crossmatchs par lymphocytotoxicité entre donneur et receveur. Il en est de même pour le typage HLA, qui peut maintenant être réalisé par séquençage en haute résolution. Néanmoins, la greffe d'organe totalement compatible reste une exception et l'apparition d'anticorps anti-HLA dans le décours de la greffe est inévitable, ce qui conditionne la survie du greffon à long terme. De nouveaux outils informatiques sont actuellement développés pour évaluer et quantifier le degré d'incompatibilité entre donneur et receveur, dans la perspective de prédire le risque de rejet et adapter la thérapie immunosuppressive de façon ciblée pour chaque patient.

[Biological markers of inflammation : an update]. / Les marqueurs biologiques de l'inflammation : faisons le point.

Biomarkers of inflammation such as sedimentation rate, C-reactive protein and procalcitonin are used in daily clinical practice for the diagnosis, prognosis and follow-up of patients with fever or inflammatory syndrome. The purpose of this article is to summarize the current knowledge about these main biological tests and to discuss new biomarkers and new assay approaches such as multiplex technology.

: Le dosage des biomarqueurs de l'inflammation, tels que la vitesse de sédimentation, la protéine-C réactive et la procalcitonine, est utilisé quotidiennement dans le cadre du diagnostic, du pronostic et du suivi des patients fébriles ou souffrant de syndrome inflammatoire. Le but de cet article est de résumer les connaissances actuelles quant à ces principaux tests biologiques et d'aborder les nouveaux biomarqueurs ainsi que les nouvelles approches de dosage comme la technologie multiplex.

[Ferritinemia, a complex marker of iron metabolism]. / La ferritinémie, un marqueur complexe du métabolisme du fer.

Ferritinemia is a basic analysis in the exploration of iron deficiency. However, its interpretation is difficult and limited due to the complexity of ferritin metabolism, which is still poorly understood, and its sensitivity to many factors, including inflammation. A more correct diagnostic approach can be obtained by combining ferritin measurement with other parameters, but at the expense of practicality. New markers should make it possible to refine the diagnosis of iron deficiency in the future.

La ferritinémie est une analyse de première ligne dans l'exploration de la carence en fer. Son interprétation est toutefois difficile et limitée en raison de la complexité du métabolisme de la ferritine, encore mal connu, et de sa sensibilité à de très nombreux facteurs dont l'inflammation. Une approche diagnostique plus correcte peut être obtenue en la combinant avec d'autres paramètres, au détriment de la praticabilité toutefois. De nouveaux marqueurs devraient permettre d'affiner le diagnostic de la carence en fer dans le futur.

[Hemophilia : a disease on the move]. / Hémophilie : une maladie en marche.

Over the last hundred years, the treatment of hemophilia has evolved considerably. To date, its principle is still to prevent the occurrence of hemorrhages by regular intravenous injections of factor VIII or IX concentrate. It allows to reach a life expectancy similar to the general population. The quality of life is constantly improving despite the constraint imposed by the modality and frequency of injections. The main complication remains the development of antibodies that inhibit the administered factors. Concentrates of long-acting factors are now available allowing to limit for example the frequency of injections. A bispecific monoclonal antibody reproducing the action of factor VIII and injectable subcutaneously has recently become available to hemophilia A patients, with the advantage of being effective even in the presence of inhibitors. Other non-substitute products are being studied offering interesting leads. Finally, gene therapy shows promising results, giving hope for access to this therapeutic option in a relatively near future. These advances are, however, a challenge for clinical laboratories, which must adapt their measurement techniques to ensure optimal monitoring. The future is on its way for hemophilia. Treatment remains expensive but it is worth the price.

Depuis un siècle, le traitement de l'hémophilie a considérablement évolué. À ce jour, son principe est toujours de prévenir la survenue d'hémorragies par injections intraveineuses régulières de concentré de facteur VIII ou IX. Il permet d'atteindre une espérance de vie similaire à la population générale. La qualité de vie est en constante amélioration, malgré la contrainte imposée par les modalités et la fréquence des injections. La complication principale reste le développement d'anticorps inhibant les facteurs administrés. Des concentrés de facteurs à action prolongée sont, maintenant, disponibles et permettent, notamment, de limiter la fréquence des injections. Un anticorps monoclonal bispécifique reproduisant l'action du facteur VIII et injectable par voie sous-cutanée est, depuis peu, à la disposition des patients hémophiles A, avec l'avantage d'être efficace même en présence d'inhibiteurs. D'autres produits non substitutifs sont à l'étude offrant des pistes intéressantes. Enfin, la thérapie génique montre des résultats prometteurs, laissant espérer un accès à cette option thérapeutique dans un futur relativement proche. Ces avancées sont cependant un défi pour les laboratoires d'analyse qui doivent adapter leurs techniques de mesure pour assurer un suivi optimal. Le futur est en marche pour l'hémophilie. Le traitement reste coûteux, mais il en vaut le prix.

[Inherited platelet disorders : clinical presentations and diagnostic algorithms]. / Diagnostic différentiel des thrombopénies et thrombopathies constitutionnelles : présentations cliniques et algorithmes décisionnels.

The diagnosis of inherited platelet disorders (IPD) is a complex task. Indeed, due to their rarity, their wide clinical spectrum (intensity of hemorrhagic symptoms) and the need for specialized biological assays (only performed in reference centers) IPDs can be diagnosed very late. However, it is important to remember the crucial need for early diagnosis in order to avoid the use of unnecessary and potentially harmful treatments for the patient. A thorough personal and family history, a complete physical examination and a simple biological work up (blood count, blood smear and platelet occlusion time) will lead to the suspicion of an IPD. It will then be up to the physician to refer the patient to a specialist in order to complete the diagnostic work up and therefore establishing a definitive diagnosis. Here is a description of the most well-known IPDs and their diagnostic algorithms.

Le diagnostic des thrombopénies et thrombopathies constitutionnelles est une tâche complexe. En effet, leur caractère rare, leur hétérogénéité clinique (intensité des symptômes hémorragiques) et la nécessité d'examens complémentaires biologiques spécialisés (uniquement réalisés dans certains centres de référence) expliquent le diagnostic parfois tardif de ces pathologies. Cependant, il convient de rappeler l'importance cruciale d'un diagnostic correct précoce pour éviter le recours à des traitements inutiles et potentiellement néfastes pour le patient en cas de thrombopénie mal diagnostiquée. Une anamnèse personnelle et familiale fouillée, un examen clinique complet et un bilan biologique de base (hémogramme, frottis sanguin et temps d'occlusion plaquettaire) permettront de suspecter une origine congénitale à la thrombopénie que présente un patient. Il reviendra alors au médecin de référer ce dernier à un spécialiste pour la réalisation d'un bilan complet visant à obtenir un diagnostic précis. Nous vous proposons ici une description des thrombopénies et thrombopathies constitutionnelles ainsi que des algorithmes pour leur diagnostic.

[How to explore Inherited platelet disorders]. / Comment j'explore Les thrombopénies et thrombopathies constitutionnelles.

Inherited platelet disorders (IPD) include a set of rare diseases whose diagnosis is often difficult because it requires the use of complex biological assays in specialized centers. They are probably under-diagnosed. Clinicians should consider an IPD when facing a chronic thrombocytopenia resistant to intravenous immunoglobulins (IVIG) and steroids together with a family history of thrombocytopenia. A syndromic thrombocytopenia will be suspected by the family survey and specific clinical signs. The confirmation of the diagnosis will then require the use of specialized biological assays such as platelet aggregation, flow cytometry, electron microscopy, platelet secretion assays, karyotype and molecular biology.

Les thrombopénies et thrombopathies constitutionnelles constituent un ensemble de pathologies rares dont le diagnostic est souvent difficile car il nécessite le recours à des analyses biologiques souvent réservées à des centres spécialisés. Elles sont probablement sous-diagnostiquées. Le clinicien devra les envisager devant une thrombopénie chronique ne répondant pas aux immunoglobulines intraveineuses et aux corticoïdes et la présence d'antécédents familiaux. Une thrombopénie syndromique sera suspectée en fonction des éléments de l'anamnèse familiale et de signes cliniques spécifiques. La confirmation du diagnostic nécessitera la réalisation d'examens biologiques spécialisés (agrégation plaquettaire, cytométrie en flux, microscopie électronique, tests de sécrétion, caryotype et biologie moléculaire).

[The Patient Blood Management]. / Le «Patient Blood Management¼ ou la «Gestion du Sang pour le Patient¼.

Patient Blood Management (PBM) is a comprehensive hospital approach to the anemic patient or at risk of becoming anemic, aimed at protecting and optimizing the patient's blood capital and resistance. The main aim of BPM is to combat the risk factors of anaemia, hemorrhage and blood transfusion. PBM involves transdisciplinary collaboration ranging from pre-hospital prevention to post-hospital follow-up. This combination of techniques and preventive actions considerably improves the medicosurgical prognosis and contributes to the drastic reduction in the use of blood transfusion. PBM is expanding worldwide and should eventually become an evolving treatment standard.

Le Patient Blood Management (PBM) est une approche hospitalière globale du patient anémique ou à risque de le devenir, visant à protéger et optimiser le capital sanguin et la résistance du patient. Le PBM vise essentiellement à lutter contre les facteurs de risques que sont l'anémie, l'hémorragie et la transfusion sanguine. Le PBM implique une collaboration transdisciplinaire qui va de la prévention pré-hospitalière au suivi post-hospitalier. Cette combinaison de techniques et d'actions préventives améliore considérablement le pronostic médico-chirurgical et contribue à la diminution drastique du recours à la transfusion sanguine. Le PBM est en extension dans le monde et devrait, à terme, devenir un standard de traitement évolutif.

Using platelet-rich plasma to treat jumper's knees: Exploring the effect of a second closely-timed infiltration.

OBJECTIVES: Some clinical series have evaluated the effect of platelet-rich plasma (PRP) in the treatment of proximal patellar tendinopathy. Although it is possible that a single infiltrative administration may prove to be an effective treatment for this indication, most of the existing studies evaluated the effects of two or three successive infiltrations. The aim of this study was to evaluate whether two infiltrations of PRP proves more effective than a single treatment. DESIGN: Prospective, randomized and comparative study of level 2. METHODS: Twenty patients suffering from chronic proximal patellar tendinopathy were enrolled into the study and split into two randomized groups (one or two infiltrations of PRP, respectively). The 3-month follow-up evaluation consisted of VAS, IKDC and VISA-P scores, along with algometer, isokinetic and ultrasounds evaluations. After 1 year, subjects were contacted to define their functional evolution. RESULTS: The concentration of the PRP used for each infiltration was similar in both groups, and contained no red or white cells. Results revealed no difference in treatment efficacy between the groups. CONCLUSIONS: The comparison between one or two infiltrations of PRP did not reveal any difference between the two groups at short to mid term. A second closely-timed infiltration of PRP to treat proximal patellar tendinopathies is not necessary to improve the efficacy of this treatment in the short term.

Simultaneous passenger lymphocyte syndrome and multiple alloimmunization against donor's blood group antigens after liver transplantation.

BACKGROUND: If 'passenger lymphocyte syndrome' (PLS) is a well-recognized complication in ABO-mismatched solid organ transplantation, the coexistence of this reaction with recipient's alloimmunization against multiple antigens expressed on the residual red blood cells in the graft is less common and unpredictable. METHODS: The receiver of an ABO minor-mismatch liver graft from a cadaveric donor developed haemolytic anaemia within 2 weeks after transplantation. The organ donor was of blood group O D+C+c+E+e+ K+k+ Le(a+b-) and the recipient, A1 D-C-c+E-e+ K-k+ Le(a-b-). The donor and recipient were both tested for irregular antibodies. Elution was performed on the recipient's red blood cells (RBCs). RESULTS: None of the recipient and donor had irregular alloantibodies at the time of transplantation. On day 10, anti-A antibodies were detected in the recipient's serum and eluted from his RBCs. At the same time, the patient developed multiple alloantibodies: anti-D, anti-C, anti-E, anti-K and anti-Le(a) against the donor's erythrocyte antigens. CONCLUSION: Although serological analysis and haemolytic parameters confirmed the diagnosis of PLS which required transfusion support, no sign of graft damage due to recipient's immune reaction was detected. This case illustrates the required follow-up of the recipient after transplantation.

Development of recombinant stable house dust mite allergen Der p 3 molecules for component-resolved diagnosis and specific immunotherapy.

BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of allergy and the safety and efficacy of immunotherapy. OBJECTIVE: The current study reports the immunological characterization of two recombinant molecules of the HDM allergen Der p 3 as useful tools for diagnosis and immunotherapy. METHODS: Recombinant mature (rDer p 3) and immature (proDer p 3) Der p 3 and their corresponding S196A mutants were produced in Pichia pastoris and purified. The stability, IgE-binding capacity and allergenicity of the different proteins were analysed and compared with those of the major mite allergen Der p 1 used as a reference. Additionally, the immunogenicity of the different allergens was evaluated in a murine model of Der p 3 sensitization. RESULTS: Compared to the IgE reactivity to recombinant and natural Der p 3 (nDer p 3), the mean IgE binding of patient's sera to rDer p 3-S196A (50%) was higher. The poorly binding to nDer p 3 or rDer p 3 was due to autolysis of the allergen. Contrary to Der p 3, proDer p 3 displayed very weak IgE reactivity, as measured by sandwich ELISA and competitive inhibition, rat basophil leukaemia degranulation and human basophil activation assays. Moreover, proDer p 3 induced a TH 1-biased immune response that prevented allergic response in mice but retained Der p 3-specific T-cell reactivity. CONCLUSION: rDer p 3-S196A should be used for the diagnosis of HDM allergy elicited by Der p 3, and proDer p 3 may represent a hypoallergen of Der p 3.

One injection of platelet-rich plasma associated to a submaximal eccentric protocol to treat chronic jumper's knee.

AIM: Jumper's knee is a frequent chronic overuse syndrome of the proximal part of the patellar tendon. Platelets contain lots of growth factors which could enhance the healing process of tendons. The aim of this study was to clarify the possible efficacy of one injection of Platelet-rich plasma (PRP) in cases of rebel jumper's knees. METHODS: Twenty patients with chronic proximal patellar tendinopathy were enrolled. Assessments were made before infiltration of PRP, and 6 weeks and 3 months after the infiltration, using a 10-point visual analogic scale of pain, clinical examinations with a pressure algometer, algofunctional scores (IKDC and VISA-P), functional assessments (isokinetic and optojump evaluations) and imagery (ultrasounds and MRI). The PRP was obtained with an apheresis system (COMTEC®, Fresenius-Kabi, Bad Homburg, Germany). Six millilitres of PRP were injected without local anesthetic. One week after infiltration, patients started a standardized sub-maximal eccentric reeducation. RESULTS: During daily activities pain significantly decreased with time. At functional evaluation, it decreased as well, but without significant functional improvement. No improvements in the imagery measurements were observed. Younger patients seemed to be more susceptible to have an improvement of pain by the PRP infiltration. CONCLUSION: This study demonstrates that a local infiltration of PRP associated with a submaximal eccentric protocol can improve symptoms of chronic jumper's knee in patients non-responsive to classical conservative treatments.

[Chronic tendinopathies and platelet-rich plasma]. / Plasma riche en plaquettes et lésions tendineuses.

Platelets contain growth factors released during their degranulation following activation. These growth factors promote tissue remodeling, wound healing and angiogenesis. Currently, the clinical effect of Platelet-Rich Plasma (PRP) is still discussed, or even controversial. Our researches have assessed the effectiveness of PRP on the healing of animal tendons and human beings suffering from chronic jumper's knee.

RISK OF RED BLOOD CELL ALLOIMMUNISATION IN RWANDA: ASSESSMENT OF PRETRANSFUSION CROSSMATCH TECHNIQUES USED IN DISTRICT HOSPITALS.

BACKGROUND: Screening of alloantibodies in patients is not yet done in district hospitals of Rwanda. The practice is to transfuse ABO/D compatible blood following an immediate spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM). OBJECTIVES: To assess the risk of red blood cell (RBC) alloimmunisation associated with the use of IS-XM compared to the IAT-XM in patients receiving blood transfusions in district hospitals in Rwanda. DESIGN: A cross-sectional comparative descriptive study. SETTING: Four Rwandan district hospitals. Kirehe and Nyanza hospitals used IS-XM while Muhima and Ruhengeri hospitals used IAT-XM. SUBJECTS: Blood samples were obtained from 187 patients (101 with IS-XM and 86 with IAT-XM) transfused in January, February, October, and November of 2012. RESULTS: The median age of blood recipients was 31 years (7 - 80) and 36% of them were male. Sixteen specific antibodies were identified in 12 patients: anti-RH1/D (2),anti-RH2/C (2), anti-RH3/E (2), anti-RH4/c (1), anti-RH5/e (2),anti-LE1/Lea (2),anti-JK1/Jka (1), anti-JK2/Jkb (1), anti-KEL1/K (1), anti-MNS1/M (1), and autoantibody (1).The global prevalence of redblood cell (RBC) alloimmunisationwas 6.4% (12/187). Thatprevalence was significantly higher in the IS-XM group (10.4%) than in the IAT-XM group (2.3%) with an odds ratio of 4.8; [95% CI=1.2-19.8]; and a p-value of 0.031. CONCLUSION: The prevalence of red blood cell (RBC) alloimmunisation in 187 patients receiving blood transfusions was 6.4% and was higher in recipients from hospitals using IS-XM, with Rhesus (RH) system antibodies widely predominant (56.2%).We recommend that IAT-XM be used in all district hospitals in Rwanda to minimise this risk.

[Oral anticoagulants: new horizons]. / Anticoagulants oraux: nouveaux horizons.

Anticoagulation is at the dawn of a new era. Dominated for a long time by heparins and vitamin K antagonists, the anticoagulant arsenal is growing up. With a direct and reversible action targeting specifically thrombin (IIa) or factor Xa, these new synthetic agents, given orally, have large therapeutic windows and predictable pharmacokinetics. Their properties allow them to avoid tight monitoring improving patient comfort and security. Pharmacological studies are promising. Regarding some indications, these new drugs seem better than "classical" anticoagulants either in efficacy or in security terms. However, they increase the hemorrhagic risk and particularly in fragile populations like elderly patients or with renal insufficiency. Only few assays are available in the laboratory to evaluate their effects and no antidote is currently on the market. The way to new anticoagulant therapies is now open. In the future, specific indications of vitamin K antagonists, heparins and these new molecules will have to be determined.

[Comparative study of five techniques of preparation of platelet-rich plasma]. / Étude comparative de cinq techniques de préparation plaquettaire (platelet-rich plasma).

AIM OF THE STUDY: Injections of platelet-rich plasma (PRP) constitute a new therapeutic for treating chronic tendinopathies. The injection being carried out in the tendon, the volume of PRP should thus be minimal (to decrease the intratendinous pressure and to minimize pain). This PRP should also have a raised platelet count. The quantity of released growth factors could be related to the system of preparation employed. We thus carried out a comparative study of five techniques of preparation of PRP described in the literature. MATERIALS AND METHODS: Samples of venous blood were taken among five patients in order to compare five techniques of preparation of PRP: University Hospital of Liège technique, Curasan(®) PRP Kit, Plateltex(®), GPS(®)II and RegenLab(®). RESULTS: The various techniques make it possible to obtain more important platelet concentration than in blood, with variable volumes (0,3 to 6ml). The number of platelets per microlitre appears higher with Plateltex(®) and obtains smallest volume of PRP. The other techniques also give small volumes except for the GPS(®)II. The number of collected platelets with this technique appears thus higher. The best collect efficiency is obtained with RegenLab(®). CONCLUSION: The technique Plateltex(®) makes it possible to collect the highest concentration of platelets in the smallest volume available.

Comparison of the platelet concentrations obtained in platelet-rich plasma (PRP) between the GPS™ II and GPS™ III systems.

INTRODUCTION: Platelet growth factors are known for their ability to speed up tissue healing (bone, skin, tendons, muscle). Various techniques make it possible to collect this platelet-rich plasma or PRP. METHODS: This study compares the platelet concentrations obtained from five patients using GPS™ III, which has recently come onto the market, with those obtained using GPS™ II. RESULTS AND CONCLUSION: We obtain a platelet concentration that is six to nine times greater with GPS ™ II and GPS™ III, but there is no significant difference between the concentrations of PRP obtained with the two systems.

[Thrombinography: towards a globalization of coagulation tests]. / La thrombinographie: vers une globalisation des tests de la coagulation.

Thrombin is the key enzyme of coagulation and thrombin generation is the central haemostatic process. Current clotting tests (PT, aPTT) measure the time at which the first fibrin filaments appear after activation of coagulation. Yet, more than 95% of thrombin is generated after clot detection, which underlies the poor sensitivity of usual clotting tests for the detection of many hemorrhagic or thrombotic diseases. Thrombinography measures the kinetics of thrombin generation and inactivation during ex vivo coagulation, in standardized conditions. Thrombin generation is reduced in hemophiliacs and in patients under anticoagulant treatment. Thrombin activity is raised in hypercoagulable states, such as antithrombin deficiency, protein C and S deficiency, factor V Leiden and in women under oral contraceptives. Thrombin generation is delayed but amplified in the presence of lupus anticoagulants. In platelet-rich plasma, thrombin generation detects thrombopathies and von Willebrand disease, and allows monitoring of antiplatelet drugs. Thrombinography allows for a global phenotype of the thrombosis-hemostasis system.

Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-kappaB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes.

Constitutive nuclear factor (NF)-kappaB activation in haematological malignancies is caused in several cases by loss of function mutations within the coding sequence of NF-kappaB inhibitory molecules such as IkappaBalpha or p100. Hut-78, a truncated form of p100, constitutively generates p52 and contributes to the development of T-cell lymphomas but the molecular mechanism underlying this oncogenic potential remains unclear. We show here that MMP9 gene expression is induced through the alternative NF-kappaB-activating pathway in fibroblasts and also on Hut-78 or p52 overexpression in fibroblasts as well as in lymphoma cells. p52 is critical for Hut-78-mediated MMP9 gene induction as a Hut-78 mutant as well as other truncated NF-kappaB2 proteins that are not processed into p52 failed to induce the expression of this metalloproteinase. Conversely, MMP9 gene expression is impaired in p52-depleted HUT-78 cells. Interestingly, MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 but not on the IkappaBalpha promoter, and the H3K4 trimethyltransferase activity recruited on the MMP9 promoter is impaired in p52-depleted HUT-78 cells. Moreover, MLL1 and MLL2 are associated with Hut-78 in a native chromatin-enriched extract. Thus, we identified a molecular mechanism by which the recruitment of a H3K4 histone methyltransferase complex on the promoter of a NF-kappaB-dependent gene induces its expression and potentially the invasive potential of lymphoma cells harbouring constitutive activity of the alternative NF-kappaB-activating pathway.