Maria Joao Baptista

Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas.

Analysis of the IGHV region in Burkitt's lymphomas supports a germinal center origin and a role for superantigens in lymphomagenesis

The analysis of immunoglobulin heavy chain variable (IGHV) region may disclose the influence of antigens in Burkitts lymphomas (BL). IGHV sequences from 38 patients and 35 cell lines were analyzed. IGHV3 subset genes were the most used and IGHV4-34 gene was overrepresented. IGHV genes were mutated in 98.6% of the cases, 36% acquired potential glycosylation sites, and in 52% somatic-hypermutation-process was ongoing. Binding motifs for superantigens like Staphylococcal protein A and carbohydrate I/i were preserved in 89% of the cases. IGHV analysis of BL cells supports a germinal center origin and points toward a role for superantigens in lymphomagenesis.

Epstein–Barr viral loads and serum free light chains levels are potential follow-up markers of HIV-related lymphomas

Maria Joao Baptista , Agueda Hernandez-Rodriguez, Eva Martinez-Caceres, Mireia Morgades, Javier Martinez-Picado , Guillem Sirera, Juan-Manuel Sancho, Evarist Feliu, Josep-Maria Ribera and Jose-Tomas Navarro Department of Hematology, ICO-Hospital Universitari Germans Trias I Pujol, Josep Carreras Leukaemia Research Institute, Universitat Aut onoma De Barcelona, Badalona, Spain; Department of Microbiology, Hospital Universitari Germans Trias I Pujol, Badalona, Spain; Division of Immunology, Hospital Universitari Germans Trias I Pujol, Badalona, Spain; Department of Cell Biology, Physiology, Immunology, Universitat Aut onoma De Barcelona, Badalona, Spain; AIDS Research Institute-IrsiCaixa, Institut D’Investigaci o En Ciències De La Salut Germans Trias I Pujol, Universitat Aut onoma De Barcelona, Badalona, Spain; Instituci o Catalana De Recerca I Estudis Avançats (ICREA), Barcelona, Spain; Department of Internal Medicine, HIV-Unit, Hospital Universitari Germans Trias I Pujol, Badalona, Spain

Using the Lymph2Cx assay for assessing cell-of-origin subtypes of HIV-related diffuse large B-cell lymphoma

Maria Joao Baptista , Gustavo Tapia, Mireia Morgades, Josep Muncunill, Ana-Mar ıa Mu~ noz-Marmol, Silvia Montoto, John G. Gribben, Maria Calaminici, Antonio Martinez , Blanca Gonzalez-Farre, Ivan Dlouhy, Eva Gonz alez-Barca, Mar ıa-Jos e Terol, Pilar Miralles, Miguel Alcoceba, Ferran Vall-Llovera, Javier Briones, Pau Abrisqueta, Eugenia Abella, Mariano Provencio, Carlos Garc ıa-Ballesteros, Jos e-Mar ıa Moraleda , Juan-Manuel Sancho, Josep-Maria Ribera , Jos e-Luis Mate and Jos e-Tomas Navarro Department of Hematology, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute (IJC), Institut Germans Trias i Pujol (IGTP), Universitat Aut onoma de Barcelona, Badalona, Spain; Department of Pathology, Hospital Germans Trias i Pujol, Universitat Aut onoma de Barcelona, Badalona, Spain; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Department of Pathology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; Department of Hematology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; Department of Hematology, ICOHospital Duran i Reynals, L’Hospitalet de Llobregat, Spain; Department of Hematology and Oncology, Hospital Cl ınic Universitari de Val encia, Valencia, Spain; Department of Infectious Diseases, Hospital Gregorio Mara~ n on, Madrid, Spain; Department of Hematology, Hospital Universitario de Salamanca, Salamanca, Spain; Department of Clinical Hematology, Hospital Universitari Mut ua de Terrassa, Terrassa, Spain; Department of Hematology, Hospital de la Santa Creu i Sant Pau, Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain; Department of Hematology, Hospital Vall d’Hebr on, Barcelona, Spain; Department of Hematology, Hospital del Mar, Barcelona, Spain; Department of Medical Oncology, Hospital Universitario Puerta De Hierro, Majadahonda, Spain; Department of Hematology, Hospital Arnau de Vilanova, Valencia, Spain; Department of Hematology, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain

Pronóstico similar de los linfomas transformados y los linfomas difusos de células B grandes de novo en pacientes tratados con inmunoquimioterapia

BACKGROUND The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. PATIENTS AND METHODS We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. RESULTS Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). CONCLUSION In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era.

Epstein-Barr virus load in plasma is an early biomarker of HIV-related lymphomas

independent prognostic marker [hazard ratio = 2.2 (95% CI, 1.3‐3.7), P < .01]. Low ACD8C and high AMC were not associated with poor OS in multivariate analysis. The OS was synergistically lower in the low ACD4C group among patients with high IPI, non‐GC DLBCL, or high AMC, respectively (the 5‐year OS was 37.2%, 48.9%, and 48.3%, respectively). The 5‐year OS rates were 81.0% and 58.7% in the high the ACD4C to AMC ratio (CD4MR) and low CD4MR groups (P < .00001). Conclusion: A low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL. The OS was synergistically lower in the low ACD4C group among patients with high IPI, non‐GC DLBCL, or high AMC, respectively.