Translational Research in Haematology

Adult cancer

SUMMARY

The creation of this unit allows speeding the transfer of scientific and medical knowledge to clinical studies, the narrow relationship between researchers, physicians and patient grants to profit of the new discoveries in blood cancers. In their initial stages, clinical trials grant the patient access to new drugs and personalised medicine.

 OVERVIEW

The Unit’s objective is to develop a line of research that will generate knowledge and new treatments for haematological cancers. It is based in the 12 de Octubre University Hospital, in collaboration with the “i+12 Research Institute”. CRIS has financed the materials and staffing needed to carry out ongoing research in the field of haematology, in order to identify new molecular targets in multiple myeloma, acute leukaemia, lymphoma and myeloproliferative neoplasms.

The unit has two departments, one for pre-clinical research and the other for patient research. The first features molecular and cellular biology laboratories with state-of-the-art instruments to allow the implementation of ground-breaking techniques in the search for new treatments.

This year, a system has been developed in the field of pre-clinical research into multiple myeloma, in collaboration with the Clinical University Hospital of Salamanca and the Biomedical Research Institute of Salamanca (IBSAL), which makes it possible to determine which patients have a higher risk of recurrence, and therefore to adjust the relevant treatment. Multiple myeloma is a difficult disease to cure: patients respond very well to treatment at first, then continue to receive maintenance therapy, and are monitored in a state known as ‘minimal residual disease’. However, the rate of successive recurrence is unpredictable. Using massive sequencing, until now restricted to basic research, it has been possible to determine the presence of tumour cells in the blood of the theoretically cured patients, which could cause the patient’s cancer to recur. This is a unique study in Europe, carried out on 133 patients in more than 80 hospitals in collaboration with the researchers of the Spanish Myeloma Group (GEM). It was published in the International Journal of Blood, and las lead to a greater understanding of the disease.

In the case of myelodysplastic syndromes, a mutation of blood cells which may lead to a type of acute leukaemia, a panel of 30 genes has been identified, which have already been studied in 80 patients to gain a better understanding of the disease and the patient’s potential progress. In Polycythemia Vera, HSP70, a new altered protein, has been discovered (M Gallardo, Mol Cancer 2013): it is a 70 Kda protein from the ‘heat shock’ group, which are very important in the folding of other proteins. Their alteration provokes a disturbance in cell function which can cause cell transformation.

Research is also being carried out into synergistic drugs which inhibit the JAK gene pathway in myelodysplastic neoplasms, a type of cancer where the bone marrow produces elevated levels of white blood cells. This work resulted in a presentation at the meeting of the American Society of Haematology.

In the field of acute lymphatic leukaemia, new mutations have been discovered in the pathways of the Jak and CRLF2 genes

In the clinical research department, the Phase I and Phase II Clinical Trials Unit is fully functioning, featuring two rooms, each with two beds, a patient and family lounge, three offices for an administrator, research staff and a data manager, and a documents archive. This Unit is authorised to carry out early clinical trials by the Community of Madrid.

The Unit actively participates in the design and development of these clinical trials and has actually managed one of these trials, which was carried out entirely in our research unit over a period of four years.

Currently, 26 Phase I and Phase II trials are taking place, 12 of which started this year; there are another 10 in the initiation stages, which include nearly 100 patients. These trials include studies of four new antibodies, cellular therapy and up to 24 different molecules, which focus on the following types of cancer:

– Systemic Amyloidosis.
– Relapsed and Refractory Acute Myeloid Leukaemia (including in children and adolescents)
– Chronic Lymphatic Leukaemia
– Acute Lymphoblastic Leukaemia
– Chronic Lymphocytic Leukaemia
– Acute Myeloblastic Leukaemia
– Chronic Myeloid Leukaemia
– Chronic Myeloproliferative Myelomonocytic Leukaemia
– Aggressive Lymphoma
– Hodgkin’s Lymphoma
– B-Cell Lymphoma
– Myelofibrosis
– Multiple Myeloma, in relapse, or treatment-resistant and in second or subsequent relapse.

The aim of these trials is to develop more effective new treatments for patients, with fewer side-effects, by:

– Studying mutations and molecular alterations and their prognostic significance in patient biopsies.
– Using pre-clinical models of haematological tumours
– Observing the molecular response to new treatments and clinical trials.
– Creating a bio-bank to allow a better study of tumours and determination of key factors in diagnosis and treatment.
– Searching for new therapeutic targets.

The future will bring further strengthening of the Unit in both the pre-clinical and clinical areas. In the former, the aims are to identify molecular targets which interrupt the process of a tumour’s genesis or progress, and then to develop molecules or cells which may be used to treat these hematopoietic cancers, and to identify new diagnostic bio-markers to allow early detection of the disease, which, through their monitoring, help to adjust the treatment to each person.

In the clinical trials department, the goals are to start Phase III trials and to continue collaboration with other disciplines and with the pre-clinical area of the University.

The CRIS Unit has also produced many high-impact scientific publications, giving a measure of the quality of the research carried out and resulting in a competitive advantage in accessing assistance programs and international clinical trials, thus facilitating the unit’s long-term goal: to help to cure cancer.