A new keyplayer in acute lymphoid leukemia
Oeiras, 01.09.2014
A team of researchers from IMM, iBET/ITQB, and IGC have opened a new route to the potential development of a therapeutic alternative for the treatment of T-cell acute lymphoblastic leukemia (T-ALL), a very frequent type of leukemia in children. The research, published in the journal Oncogene, studied the role of a particular protein (CHK1) in patients and concluded that it is over expressed and hyper activated, thereby enabling the viability and proliferation of tumor cells.
The researchers used a pharmacological compound (PF-004777736) to inhibit CHK1 in cell cultures and found that the compound induced the death of T-ALL cells without affecting normal T-cells. They further observed that the use of this drug compound is capable of interfering with the in vitro proliferation of the leukemic cells and to disrupt their life cycle, reducing the development of the disease. Although this type of leukemia has a great therapeutic success in children, side effects of current therapies are quite substantial. The research work led by the IMM team may lead to an increase in the effectiveness in the fight against this disease.
T-cell acute lymphoblastic leukemia (T-ALL) is a blood cancer particularly common in children, characterized by an uncontrolled increase in the number of T lymphocytes (white blood cells), cells of the immune system responsible for specifically recognizing and neutralizing agents causing external infection. T cells are produced in the bone marrow and are usually in the bloodstream. The incidence of ALL in general (which also includes cases affecting B lymphocytes) is relatively similar in Europe and the United States of America, with one case per 50,000 inhabitants. Although quite common in children it is a rare type of cancer and its treatment has an efficiency, which allows around 80 percent survival rates after five years. The 10-20% of cases with recurrence present extremely poor prognosis with less than 20% chance of cure. Furthermore, a major problem is that even in case of cure the extent of the side effects can be quite large and extend into adulthood, including cognitive and growth delay, endocrine problems, increased probability of secondary tumors, and/or obesity.
Original Article
Oncogene. 2014 Aug 18;0. doi: 10.1038/onc.2014.248
CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for proliferation and survival by preventing excessive replication stress.
Leonor Morais Sarmento1, Vanda Póvoa1, Rute Nascimento2, Gonçalo Real3, Inês Antunes1, Leila Martins1, Catarina Moita1, Paula M. Alves3, Miguel Abecasis4, Luís Moita1, Robert M. Parkhouse2, Jules Meijerink5 and João Taborda Barata1
1-Instituto de Medicina Molecular, Faculdade de Medicina, Universidada de Lisboa, Lisbon, Portugal.
2-Infections and Immunity Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
3-[1] iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal [2] Instituto de Tecnologia Química e Biológica, Oeiras, Portugal.
4-Cardiologia Pediátrica Medico-Cirúrgica, Hospital Sta. Cruz, Carnaxide, Lisbon, Portugal.
5-Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
