RESUMEN
Background: With the introduction of the anti-CD20 antibody rituximab, the outcome of patients with follicular lymphoma (FL) has greatly improved over the last two decades. First-line prolonged rituximab monotherapy is effective, achieving long-term remission and prolonged failure-free survival in some patients. Additionally, rituximab has been shown to synergize with chemotherapeutic and novel targeted agents alike with measurable gains in duration of response. As such, rituximab has made its mark in the treatment of FL and remains a valid agent despite the availability of newer monoclonal antibodies. This review summarizes the evolving role of rituximab as the first available anti-CD20 monoclonal antibody, emphasizing its clear activity as a single agent and in combination with chemotherapy or molecular targeted agents, and setting the standard for the development of new anti-CD20 monoclonal antibodies. Conclusion: We provide data that support the ongoing use of rituximab as a therapeutic partner for novel agents in future clinical trials exploring chemotherapy-free alternatives.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , HumanosRESUMEN
Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cß. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.
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Leucemia de Células B/tratamiento farmacológico , Purinas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Quinazolinonas/uso terapéutico , Receptores de Antígenos de Linfocitos B/efectos de los fármacos , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Piperidinas , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Quinazolinonas/administración & dosificación , Macroglobulinemia de Waldenström/tratamiento farmacológicoRESUMEN
Ibrutinib (Imbruvica™) is an irreversible, potent inhibitor of Bruton's tyrosine kinase (BTK). Over the last few years, ibrutinib has developed from a promising drug candidate to being approved by FDA for the treatment of three B cell malignancies, a truly remarkable feat. Few, if any medicines are monospecific and ibrutinib is no exception; already during ibrutinib's initial characterization, it was found that it could bind also to other kinases. In this review, we discuss the implications of such interactions, which go beyond the selective effect on BTK in B cell malignancies. In certain cases, the outcome of ibrutinib treatment likely results from the combined inhibition of BTK and other kinases, causing additive or synergistic, effects. Conversely, there are also examples when the clinical outcome seems unrelated to inhibition of BTK. Thus, more specifically, adverse effects such as enhanced bleeding or arrhythmias could potentially be explained by different interactions. We also predict that during long-term treatment bone homoeostasis might be affected due to the inhibition of osteoclasts. Moreover, the binding of ibrutinib to molecular targets other than BTK or effects on cells other than B cell-derived malignancies could be beneficial and result in new indications for clinical applications.
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Trastornos Linfoproliferativos/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa , Animales , Fibrilación Atrial/inducido químicamente , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Ratones , Mieloma Múltiple/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Piperidinas , Unión Proteica , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Macroglobulinemia de Waldenström/tratamiento farmacológicoAsunto(s)
Oncología Médica/normas , Recurrencia Local de Neoplasia/terapia , Medicina de Precisión/normas , Sociedades Médicas/normas , Macroglobulinemia de Waldenström/terapia , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Edad de Inicio , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Asintomáticas/terapia , Médula Ósea/patología , Europa (Continente) , Humanos , Incidencia , Oncología Médica/métodos , Factor 88 de Diferenciación Mieloide/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Plasmaféresis/métodos , Plasmaféresis/normas , Medicina de Precisión/métodos , Receptores CXCR4/genética , Trasplante de Células Madre/métodos , Trasplante de Células Madre/normas , Supervivencia , Trasplante Autólogo/métodos , Trasplante Autólogo/normas , Resultado del Tratamiento , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/epidemiología , Macroglobulinemia de Waldenström/patologíaRESUMEN
To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma. The consensus conference convened â¼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence. This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.
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Leucemia Linfocítica Crónica de Células B/terapia , Linfoma Folicular/radioterapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Manejo de la Enfermedad , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Guías de Práctica Clínica como Asunto , Trasplante de Células MadreRESUMEN
The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/- interferon).
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Linfoma Folicular , Humanos , Rituximab , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/genética , Variaciones en el Número de Copia de ADN , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Interferones/uso terapéutico , Biopsia , Expresión GénicaRESUMEN
Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.
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COVID-19 , Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/prevención & control , Macroglobulinemia de Waldenström/diagnóstico , Vacunas contra la COVID-19 , Consenso , SARS-CoV-2 , Antivirales/uso terapéuticoRESUMEN
Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.
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Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/genética , Rituximab/uso terapéutico , Consenso , Ciclofosfamida/uso terapéutico , Clorhidrato de Bendamustina/uso terapéuticoRESUMEN
We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.
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Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular , Protocolos de Quimioterapia Combinada Antineoplásica , Autoinjertos , Terapia Combinada , Estudios de Seguimiento , Humanos , Linfoma Folicular/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Prospectivos , Estudios Retrospectivos , Rituximab/uso terapéutico , Trasplante AutólogoAsunto(s)
Anticuerpos Monoclonales/sangre , Inmunoglobulina M/sangre , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/terapia , Antineoplásicos/uso terapéutico , Células de la Médula Ósea/citología , Europa (Continente)/epidemiología , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estadificación de Neoplasias , Medición de Riesgo , Resultado del Tratamiento , Macroglobulinemia de Waldenström/epidemiologíaRESUMEN
The aim of this project was to identify situations where allogeneic stem cell transplantation (allo-SCT) might be considered as a preferred treatment option for patients with B-cell chronic lymphocytic leukemia (CLL). Based on a MEDLINE search and additional sources, a consented proposal was drafted, refined and approved upon final discussion by an international expert panel. Key elements of the consensus are (1) allo-SCT is a procedure with evidence-based efficacy in poor-risk CLL; (2) although definition of 'poor-risk CLL' requires further investigation, allo-SCT is a reasonable treatment option for younger patients with (i) non-response or early relapse (within 12 months) after purine analogues, (ii) relapse within 24 months after having achieved a response with purine-analogue-based combination therapy or autologous transplantation, and (iii) patients with p53 abnormalities requiring treatment; and (3) optimum transplant strategies may vary according to distinct clinical situations and should be defined in prospective trials. This is the first attempt to define standard indications for allo-SCT in CLL. Nevertheless, whenever possible, allo-SCT should be performed within disease-specific prospective clinical protocols in order to continuously refine transplant indications according to new developments in risk assessment and treatment of CLL.
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Leucemia Linfocítica Crónica de Células B/terapia , Trasplante de Células Madre , Adolescente , Adulto , Factores de Edad , Medicina Basada en la Evidencia , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/fisiopatología , Persona de Mediana Edad , Pronóstico , Recurrencia , Factores de Riesgo , Factores de TiempoRESUMEN
PURPOSE: Purine analogs have wide potential indications in the treatment of hematologic malignancies, but intravenous administration has been required. We previously established that the oral bioavailability of cladribine is 50%. Our aim was to evaluate the efficacy and toxicity of oral cladribine to previously untreated patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Sixty-three patients with symptomatic but previously untreated CLL received cladribine solution 10 mg/m2/d orally for 5 consecutive days in monthly courses. RESULTS: Complete remission (CR) was achieved in 24 patients (38%), and 23 patients (37%) had a partial response (PR). Most patients, including those in whom there was no remission (NR) achieved normal blood lymphocyte counts. Failure to meet response criteria was mostly due to thrombocytopenia. The median response duration was not reached at 2 years. The median survival time among 13 deceased patients was 322 days, whereas the median observation time of surviving patients is 760 days. The overall survival rate at 2 years is 82%. Response rate was associated with clinical stage. Grade III to IV infectious toxicity occurred in one third of patients. CONCLUSION: Orally administered cladribine is an effective and feasible therapy for CLL, and produces durable remissions in three quarters of the patients. However, significant toxicity may occur and further studies are required to assess long-term effects and quality-of-life aspects.
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Antineoplásicos/administración & dosificación , Cladribina/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Administración Oral , Anciano , Antineoplásicos/efectos adversos , Recuento de Células Sanguíneas , Cladribina/efectos adversos , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/mortalidad , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
Acute myeloid leukemia preceded by a myelodysplastic syndrome (MDS-AML) is generally regarded as a high-risk type of AML, where remissions are rare and of short duration. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is suggested to increase the sensitivity of leukemic cells to cycle-specific drugs. In this study 14 MDS-AML patients were given rhGM-CSF together with standard induction chemotherapy (TAD). rhGM-CSF was started 48 h prior to chemotherapy and given for up to 3 weeks. The results showed eight (58%) complete and two (14%) partial remissions, while another two (14%) patients had minor responses. One patient relapsed after 1 year, and then responded a second time. rhGM-CSF had to be stopped owing to local allergic reactions in two patients, both non-responders, but was otherwise well tolerated. Compared with our historical group of controls we found significantly higher remission rates, fewer early deaths, fewer fever days, and fewer days with both neutropenia and thrombocytopenia among the patients treated with rhGM-CSF and TAD. The estimated median over-all survival was 332 days. The severity of initial myelodysplastic changes did not correlate to the outcome of therapy but the degree of peripheral blood dysplasia decreased among responding patients. MDS-AML patients in this pilot study did respond better, and with minimal toxicity, when standard induction chemotherapy was given in combination with rhGM-CSF.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/patología , Anciano , Terapia Combinada , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Proteínas Recombinantes/uso terapéutico , Inducción de Remisión , Tioguanina/administración & dosificaciónRESUMEN
T and NK cell blood subpopulations were determined in 33 patients with B-CLL and in 14 patients with B-MLUS by two-color immunofluorescence. CLL patients had significantly higher total numbers of Leu-7+ and CD8+ cells and lower numbers of CD16+/Leu-7- cells as well as a higher Leu-7/CD16 ratio and a lower CD4/CD8 ratio than MLUS patients and control donors. Moreover, MLUS patients exhibited a significantly lower Leu-7/CD16 ratio as well as a higher frequency of CD16+/Leu-7- cells than healthy donors. These results suggest that B-CLL patients have higher numbers of circulating immature NK cells compared to B-MLUS, while B-MLUS patients have a larger proportion of NK cells with a high lytic capability as compared to both CLL and normal controls. The imbalance between CD4+ and CD8+ cells was prominent in CLL with a low CD4/CD8 ratio, but within the upper normal range in MLUS. Differences in immunoregulatory cell subpopulations between B-CLL and B-MLUS might therefore contribute to the different clinical behavior of these two disorders.
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Linfocitos B/inmunología , Células Asesinas Naturales/clasificación , Leucemia Linfocítica Crónica de Células B/sangre , Linfocitosis/sangre , Linfocitos T/clasificación , Adulto , Anciano , Antígenos de Diferenciación , Células Clonales/inmunología , Femenino , Humanos , Células Asesinas Naturales/análisis , Leucemia Linfocítica Crónica de Células B/inmunología , Recuento de Leucocitos , Linfocitosis/inmunología , Masculino , Persona de Mediana Edad , Fenotipo , Coloración y Etiquetado , Linfocitos T/análisisRESUMEN
The fraction of blood S-phase (S+) lymphocytes from 41 patients with chronic lymphocytic leukemia of B cell type was determined by flow cytometry. The patients were grouped according to the smig isotype pattern of the leukemic cells. Patients with IgM as the predominant smig had higher numbers of S+ lymphocytes than patients with a leukemic clone co-expressing IgM and IgD (p less than 0.001). High relative as well as total numbers of S+ lymphocytes were associated with short therapy-free and overall survival. T cell proliferation was low although significantly higher in active than in indolent disease.
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Isotipos de Inmunoglobulinas/análisis , Interfase , Leucemia Linfoide/patología , Receptores de Antígenos de Linfocitos B/análisis , Linfocitos B/inmunología , Linfocitos B/patología , ADN de Neoplasias/análisis , Humanos , Cadenas delta de Inmunoglobulina/análisis , Cadenas mu de Inmunoglobulina/análisis , Leucemia Linfoide/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Factores de TiempoRESUMEN
Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia (CLL). The chimeric status of the six patients studied was further investigated with minimal residual disease (MRD) detection, by sequencing and using patient-specific primers derived from junctional regions of clonally rearranged immunoglobulin heavy-chain (IgH) receptor genes. To date, five of six patients are alive with a median follow-up time of 24 months (range 15-60) post-SCT. All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT. All patients were MRD positive after SCT, which correlated to mixed chimerism within the CD19+ cell fraction in all samples except one (25/26). High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT. Hence, a high tumor burden pre-SCT may reflect the long duration of detectable MRD in patients with B-CLL after SCT. A durable anti-leukemic effect was probably important in these patients.
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Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/terapia , Adulto , Médula Ósea/metabolismo , Femenino , Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoglobulinas/genética , Leucemia Linfocítica Crónica de Células B/sangre , Masculino , Persona de Mediana Edad , Neoplasia Residual/prevención & control , Reacción en Cadena de la Polimerasa , Receptores de Interleucina-2/sangre , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Trasplante Homólogo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Mantle cell lymphoma (MCL) is a moderately aggressive B-cell lymphoma that responds poorly to currently used therapeutic protocols. In order to identify tumour characteristics that improve the understanding of biology of MCL, analysis of oligonucleotide microarrays were used to define specific gene expression profiles. Biopsy samples of MCL cases were compared to reactive lymphoid tissue. Among genes differentially expressed in MCL were genes that are involved in the regulation of proliferation, cell signalling, adhesion and homing. Furthermore, some genes with previously unknown function, such as C11orf32, C2orf10, TBC1D9 and ABCA6 were found to be differentially expressed in MCL compared to reactive lymphoid tissue. Of special interest was the high expression of the cannabinoid receptor 1 (CB1) gene in all MCL cases analysed. These results were further confirmed at the cellular and protein level by immunocytochemical staining and immunoblotting of MCL cells. Furthermore, there was a reduced expression of a regulator of G protein signalling, RGS13 in all MCLs, with a complete absence in the majority of cases while present in control lymphoid tissue. These results were further confirmed by PCR. Sequencing of the RGS13 gene revealed changes suggesting polymorphisms, indicating that downregulation of the expression of RGS13 is not related to mutations, but may serve as a new specific marker for MCL. Moreover, comparison between individual cases of MCL, revealed that the CCND1 gene appears to be differently expressed in MCL cases with high vs low proliferative activity.