24 Nov, 2020

Acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). It can sometimes spread to the brain and spinal cord, and for this reason, patients may need to have a sample of their spinal fluid removed for testing using a lumbar puncture – also known as a spinal tap.

Possible risk factors for ALL include being male, Caucasian, older than 70, having previously undergone chemotherapy or radiation therapy for cancer, having been exposed to high levels of radiation in the environment (such as nuclear radiation) or having certain genetic  disorders such as Down syndrome.  However, ALL can also affect children and is, in fact, the most common type of malignancy in children,

Signs and symptoms include fever, tiredness and easy bruising or bleeding. This type of cancer usually gets worse quickly if it isn’t treated. Normally, the bone marrow produces blood stem cells (immature cells) that become mature blood cells over time.

In ALL, too many stem cells – which are also called leukemia cells – are unable to fight infection very well. Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells and platelets, resulting in infection, anemia and bleeding. The leukemia cells may build up in the cerebrospinal fluid surrounding the spine and brain or take up residence in the actual brain.

Now, Israeli and Scottish researchers have achieved a breakthrough that could influence treatment of ALL spreading to the brain. An international research group from Schneider Children’s Medical Center in Petah Tikva and Tel Aviv University (TAU), together with researchers from the Technion-Israel Institute of Technology in Haifa and the University of Glasgow in Scotland has reported in Nature Cancer (entitled “Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase”) on their important findings based on mouse models.

The work was carried out by three young female scientists: Dr. Angela Maria Savino from Prof. Shai Izraeli’s lab in the hematology-oncology department at Schneider’s and and TAU’s Sackler Faculty of Medicine; doctoral student Sara Isabel Fernandes from the lab of Prof. Eyal Gottlieb from the Rappaport Institute and Rappaport Faculty of Medicine at Technion; and Dr. Orianne Olivares from the lab of Prof. Christina Halsey at the University of Glasgow.

The team, which included hematological and oncological experts, discovered that a drug that thwarts the production of fatty acids can block the spread of leukemia to the brain.

Their research focuses on acute lymphoblastic leukemia (ALL), which is. Although the recovery rates for this disease are relatively high, the treatment is harsh and accompanied by numerous side effects that can persist years after the patient is cured.

Since one of the main risks of ALL is that the cancer will metastasize to the brain, children diagnosed with this disease receive a prophylactic treatment that protects the brain from metastasized cells. Currently, this treatment consists of injecting chemotherapy drugs into the spinal fluid and sometimes also radiation to the skull, which carries the risk of side effects for damaged brain function since these chemotherapy drugs also harm healthy brain cells. For this reason, a worldwide effort is underway to develop more selective treatments that will only affect the leukemia cells and not the brain cells. The current research reveals for the first time that the solution lies in fatty acids.

Fatty acids are an essential resource for cells, including leukemia cells. Leukemia cells obtain sufficient fatty acids in the bone marrow and blood, but when they travel to the brain in a metastatic process, they reach an area that is very poor in fatty acids. According to the recently published research, for them to continue to thrive and flourish in the brain, the ALL cells develop an ability to produce fatty acids on their own.

Based on these findings, the researchers reached the conclusion that treating the patient with drugs that block the production of fatty acids will prevent the leukemia cells from producing fatty acids and will thereby “starve” them and stop them from flourishing in the brain. Indeed, the use of such drugs in mice has stopped the spread of metastatic leukemia to their brains.

The drugs used in the current research are still being developed and therefore not yet approved for use in humans, but the research findings provide hope for more precise treatment that will most likely be less toxic for preventing the spread of leukemia to the brain.

The research findings are also relevant for several other types of cancer in children and adults in addition to ALL, since most deaths from cancer are not caused by the primary tumor but rather by the spread of metastasized cells to distant organs. This research, which demonstrates that cancer cells adapt to the organs to which they spread, paves the way for biological treatments that block these adaptation mechanisms, thereby stopping the cancer cells from metastasizing.