How does leukemia develop? The molecular cause has now been identified in two studies.
Severe congenital neutropenia (CN) is a precancerous bone marrow failure syndrome that progresses to Acute myeloid leukemia (AML) can develop.
Immunodeficiency with low granulocyte count
This rare congenital hematopoietic disorder is one HIVWith a reduced number grains And functional defects associated with it. Serious bacterial infections occur in sufferers early after birth. The only possible treatment is lifelong treatment with recombinant growth factors (proteins), which must be injected daily. 20% of patients are congenital Neutrophils Suffer from leukemia in the first decades of life.
A team of researchers at the University Hospital Tübingen have now succeeded in shattering the mechanism by which leukemia develops and in exploring a new treatment. As Head of the Reference Laboratory for Diagnosis and Research of the International Registry of Severe Chronic Neutropenia (SCNIR), Professor Julia Squawah has been able to collect large amounts of data from patients with rare diseases of her. Research project analyzing.
A new test model has been developed
Due to the lack of animal models of neutropenia and the difficulty in obtaining sufficient bone marrow cells from patients, researchers have developed a new type of experimental model to study leukemia. They use molecular methods to restore the blood cells of patients with neutropenia to an early fetal state – to induced pluripotent stem cells (IPS cells).
In cell cultures, they in turn generate hematopoietic cells from these stem cells. Using a new method, genetic clipper (CRISPR / Cas9), they made the malignant leukemia cell and added the gene mutation to the iPS cells. Experts have succeeded in producing leukemia cells in cell cultures that closely resemble the primary leukemia cells of patients with neutropenia.
BALC causes the leukemia cells to die
The researchers also studied the effects of those genes in which leukemia cells contained significantly greater amounts of healthy cells. To investigate this effect on leukemia growth, genes in stem cells generated in vitro were stopped using gene scissors.
It has been discovered that turning off a single protein – PLC It leads to the death of leukemia cells. By analyzing the activation of all BAALC-dependent genes, Skokowa and her team were able to decipher the molecular mechanism of leukemia development and to identify a low molecular weight inhibitor (CMPD1) with therapeutic effects. This new drug kills leukemia cells without attacking normal blood-forming cells, so it could be used to treat leukemia in clinical studies.
Image source: Professor Osaru Erhapour, Wikimedia Commons