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Applied clinical research in hematological malignances Beatriz Bellosillo

Molecular markers in chronic myeloproliferative disorders

JAK2 mutations have been recently described in chronic myeloproliferative disorders (95% of polycythaemia vera, 50-60% of essential thrombocythemia, 50-60% of primary myelofibrosis).

The objectives of our study are:

• To determine the role of JAK2 as a molecular marker in the follow-up of these patients
• To monitor response to cytoreductive treatment in essential thrombocythemia
• To search for new mutations in CMD patients which are negative for JAK2 V617F
• To analyse the JAK/STAT signal transduction pathway in essential thrombocythemia patients
• To search for new mutations in polycythemia vera 

Analysis of apoptotic pathways in response to treatment in marginal zone lymphoma.

The aim of these study is to perform in vitro cultures with neoplastic lymphoid cells obtained from patients with MALT lymphoma and to analyse the effect of drugs commonly used in lymphoma treatment (rituximab, fludarabine, bortezomib). The objectives are:

• To analyse patient sensitivity profile to the different drugs
• To determine genetic factors involved in sensitivity/resistance
• To study the signal transduction pathways involved in drug cytotoxicity

Characterization of minimal residual disease and role of regulatory T cells in gastric MALT lymphomas

MALT lymphomas of the stomach are neoplasm associated to antigenic stimulation by chronic infection by H. pylori. Regulatory T cells (T reg cells) are associated with autoimmune disorders and some types of cancer. Studying the role of T reg cells in gastric MALT lymphoma would allow us a better understanding of the pathogenesis of these tumours and, at the same time, to design a more rational therapeutic approach in cases without association to H. pylori infection and in patients with refractory disease.

Objectives: 

• To study by immunohistochemistry the expression of T reg cells in the microenviroment of the tumor in gastric MALT lymphomas at the time of diagnosis and during follow-up. 
• To evaluate the association between histologic response and minimal residual disease (MRD) in gastric bipsies of MALT lymphomas, associated or not to H. pylori infection. 
• To compare the expression of T reg cells with the detection of MRD by histology and molecular techniques. 
• To study the clinical significance of the detection of MRD in gastric MALT lymphomas and its potential impact with respect to the endoscopic follow-up.

Methods: 

• To analize the expression of T reg cells in the microenvironment of the tumor through immunohistochemistry with FOXP3 in paraffin samples of gastric MALT lymphomas at the time of diagnosis and during the follow-up. 
• Clonality study of the B cell receptor according to the BIOMED-2 protocol and detection of API2/MALT1 by RT-PCR at diagnosis. 
• Study of MRD through analisis of rearrangement of B cell receptor (BIOMED-2 protocol) and API2/MALT1 by RT-PCR in the follow-up of gastric MALT lymphomas, and to analize its impact in clinical management. 
• Data collection in a data base and subsequent statistical analysis.

Primary breast cancer cultures.

Drug effects on breast cancer cells are usually tested on cell lines. These provide important and reproducible results, but have the limitation that are cells transformed and not always equivalent to tumoral cells from patients. The objectives of this research project are:

• To establish ex vivo cultures of breast cancer cells
• To evaluate the effect of several chemotherapeutic drugs
• To analyse predictive biomarkers and perform pharmacodynamic studies with this model.