An expert group Molecular Immunology Group at the University of Granada (UGR) is checking the effectiveness of a combination of drugs and substances produced by the body that act against the cells affected by leukemia, without causing adverse effects on healthy cells.

In a statement, Andalucia Innova indicated that this combined treatment comprises both the body’s own substances (endogenous) and exogenous.

Cancer is characterized by a malfunction of the cells, and proliferate in an uncontrolled way and “do not die when they should,” which is due to alterations in the genes that regulate growth and cell death.

In this regard, the researchers from Granada are focusing their efforts in studying internal dysfunctions and the search for drugs to restore normal function. The team uses substances that reverse these modifications, for the cell to properly regulate and stop proliferating.

In addition, these drugs, called inhibitors of DNA methylation, provoke the cell death (apoptosis) affected by cancer. “These inhibitors, by themselves, induce apoptosis in leukemia cells and also selectively without harming normal cells. This allows us to develop new drugs that do not exert any toxicity to the body,” explained project leader Maria del Carmen Ruiz.

Moreover, experts combine inhibitors of epigenetic modifications, called histone deacetylase inhibitors, with a molecule called Trail, which the body produces naturally and is expressed in certain immune system cells, which also causes the selective death of tumor cells without being affected normal.

“We added this molecule with synthetic inhibitors and found that the combination of both substances induces cell death and thus improves the antitumor effect,” said Ruiz, who added that they are testing different methods of administering Trail, either through exogenous addition or increasing production by cells of the body itself.

For now, researchers are using these substances in the laboratory cell cultures and blood samples of patients suffering from leukemia. However, the project leader said “the high selectivity of this combination of drugs to tumor cells makes it very attractive for future application in the treatment of cancer.”

The work involves a study of the National Plan, financed by the Carlos III Health Institute with a budget of EUR 148 830.

A team at the Consejo Superior de Investigaciones Científicas (CSIC) has discovered the mechanism by which the enzyme MMP-9 affects the survival of cells of B chronic lymphocytic leukemia (CLL-B) and allows the spread of the disease.

The finding, which appears in the February issue of the journal Cancer Cell, explains why they have failed the clinical trials have been conducted targeting this enzyme and defines a potential strategy for the design of future treatments for disease.

As explained by the director of research, Angeles Garcia Pardo, a research professor of the CSIC, B-CLL is characterized by the accumulation of abnormal B lymphocytes in peripheral blood, which circulates throughout the body.

As the disease progresses these cells are distributed throughout the body via the blood and reach lymphoid organs, such as bone marrow and lymph. This prevents the normal functioning of normal B cells, vital components of the defensive line of human beings, and the action of the disease results in death.

Garcia Pardo and his team of the CSIC in Madrid with the collaboration of hematologists University Hospital Puerta de Hierro in Madrid, and the Clinical Hospital of Valencia, as well as with scientists from the University of Louvain (Belgium), Justus Liebig University (Germany).

The group has studied the mechanisms involved in migration and survival of B-CLL cells, ie the processes that lead to disease spread. Have focused on matrix metalloproteinase-9 (MMP-9), an enzyme that degrades the extracellular matrix, the medium in which cells are embedded, which facilitates the progress of B-CLL cells.

Along with this capability, already known to degrade substrates and pave the way for the disease, the CSIC group have discovered a new role for MMP-9: to ensure the survival of B-CLL cells, through binding to specific receptors on its membrane and induction of intracellular signals. This new feature does not require the enzymatic activity of MMP-9, but is located in another region of the molecule, called hemopexin domain.

“The finding is relevant because, so far, clinical trials have been to placate the action of MMP-9 enzyme that degrades substrates and have not had the expected success. Our work provides an explanation for these failures and define the region cell which produces the connection between MMP-9 and malignant cells as a new target for the design of treatments against this leukemia, “he concludes.

For hematopoietic progenitor cells (blood stem cells able to repopulate the bone) ‘enough’ to refer to the donor pre-treatment to multiply the presence of these units in their blood and then extract and implant in a patient with leukemia or other haematological malignancies.

As explained by Dr. Javier Lopez, a hematologist at the Hospital Ramón y Cajal de Madrid, the peripheral blood has an advantage over bone marrow, which is that “offers a faster recovery,” because it takes less time to ‘catch’. So, now usually opt for this technique to treat patients with advanced leukemia, to ensure that your bone marrow recover quickly. While in patients with less advanced disease, is chosen by the bone marrow, which takes a few more days at work in exchange for offering a better safety profile.

In order to clarify the differences between the two methods in the long term, the European Group for Blood and Marrow Transplantation (from Germany led by Dr. Birte Freidrichs) has compared the evolution of 329 patients with various types of leukemia treated both transplants across Europe between 1995 and 1999.

After a median follow-up 10 years (the most extensive to date), the researchers found no difference in the prognosis of survival with bone marrow or peripheral blood (donated by both brothers supported.) In fact, they add, although patients treated with this technique were more complications of rejection (the so-called graft versus host disease), this problem did not result in more deaths.

In patients with acute leukemia, there was a trend of survival better (although not statistically significant) in bone marrow transplant with peripheral blood. Only in chronic myeloid leukemia were more positive results with peripheral blood. “These findings suggest that there is a subgroup of patients who may benefit even bone marrow transplantation.”

“After a decade of monitoring, increased incidence of graft-versus-host disease did not result in a greater number of deaths, nor affected the overall health of patients, nor their social integration, complete these European hematologists . In his view, the results do not allow to conclude for themselves that it is time to return to bone marrow transplants for certain indications, but that this technique can not be parked entirely at the moment.

A new molecular tool could become a therapeutic option for acute myeloid leukemia.

According to a study published in the latest issue of Cell Stem Cell, preclinical studies conducted by a team from Children Cancer Institute Australia have demonstrated that CD123 molecule is over expressed in leukemia stem cells, whereas its expression in healthy cells is normal.

This molecule is part of the interleukin-3 receptor, a protein that interacts with a growth factor linked to survival and cell proliferation.

The creation of a monoclonal antibody that binds to CD 123 for attempting to interfere selectively in the survival of leukemia stem cells is the main innovation offered by the work coordinated by Richard Lock.

When tumor stem cells were transplanted into mice treated with the antibody, known as 7G3, cytokine signaling in cancer cells was blocked.

In addition, 7G3 inhibited the migration of leukemia stem cells in the marrow and activated the innate immune system of animals to destroy diseased cells.

U.S. scientists published in The New England Journal of Medicine have succeeded in reversing the disease in 9 of 10 patients treated with a new procedure.

The preliminary study results show that the “mini” stem cells could reverse the severe sickle cell anemia in adults, according to a study by the NIH and Johns Hopkins University (USA), which is published today in The New England Journal of Medicine.

The phase I / II describes 10 patients with severe sickle cell disease who received intravenous transplants of hematopoietic stem cells, peripheral blood from healthy unrelated donors, which were adapted to tissue types of patients.

When the scientists used this procedure, 9 of the 10 patients showed normal red blood cells and recovery of organ damage caused by the disease.

Jonathan Powell explains, “the method of intravenous transplantation for sickle cell anemia, caused by a single mutation in the gene for hemoglobin, does not replace the defective gene but transplanted blood stem cells carrying the normal gene.

All patients in the study, from 16 to 45 years of age, were treated at the NIH with a “mini” and an immune suppressant drug, rapamycin.

Conventional transplantation methods using high doses of chemotherapy to suppress the immune system before injecting the transplanted cells, a process that has many side effects, including contracting serious bacterial infections that could kill patients. In the “mini” are used lower doses of medication and radiation to allow the arrival of the donated cells.

As pointed out by Powell, side effects were less and very mild compared with bone marrow transplantation. In 9 of the 10 patients, the donated cells now coexist with the patient.

The “mini” for sickle cell anemia patients were tested in nearly a decade ago and were not successful because the immune system from rejecting the transplanted cells affected. However, Powell indicated that the use of rapamycin promotes the coexistence of the donated cells to the patient.