What are genetic mutations and how do they relate to AML?

What are genetic mutations?

Leukemia is a cancer of the bone marrow. And the bone marrow are these stem cells that are responsible for making all of our blood cells, the red blood cells that carry oxygen, the white blood cells that fight infection, and the platelets that clot the blood.

And in order to be these different types of cells, a metabolic stem cell, a bone marrow stem cell needs to read the genetic information inside the cell and turn on genes that are important for its lineage specification, for what type of cell it's ultimately going to be, and turn off other genes that are unnecessary.

genetic mutations are abnormalities in the DNA of cells that when they occur they make the cell become leukemic. So you can imagine you have a whole bunch of normal cells in your bone marrow. And when one of those cells is dividing, something goes wrong. Where a mutation, meaning a change in the DNA of that cell develops, that change in the DNA, if it's the right change in the right gene, or maybe in the wrong gene is the better way to say it. What ends up happening is that that cell becomes malignant, that cell becomes cancer, and when that cell becomes cancer, it, has a propensity to grow and grow and grow and have unbridled growth. And that's really what all cancer is forget about leukemia or acute myeloid leukemia. But all cancer is the inability of a cell to stop growing and stop dividing.

How do mutations in leukemia cells differ from normal cells in AML patients?

What happens in many types of cancer is there is some sort of alteration or mutation in the actual instruction manual. The genetic code that mutation changes the way that that stem cell is able to respond and effectively turn on the right genes.

And so what ends up happening sometimes is there are really two sort of classes, classically that we think of with regards to genetic abnormalities in all cancers, but in particular leukemia, there are mutations that turn on a gene that's responsible for growth and cell division. We call those are oncogenes. The metaphor most commonly used a gas pedal that's stuck to the floor. These cells now continue to grow without respect to the instructions of the environment around it. Those instructions are really important. If somebody was bleeding, they would need to make lots more red blood cells to replace them. So that gas pedal functions really important. If somebody had an infection, you want to make more white blood cells. So that gas pedal functions really important.

The other class or what we call tumor suppressor genes that metaphor again using the the car is that the brake pedal doesn't work. And so these check-points that a cell would go through to make sure that the DNA has copied properly and that the cell is ready for division now or bypassed. And so typically this can result in the wrong genes being expressed or more commonly, the cell will go through a cell division without picking up some of the mistakes or the challenges.

All these mutations, all of this genetic information is changing the way that that bone marrow stem cell is able to function, and now it no longer can differentiate or mature into the types of cells it needs to be. And it starts to grow irrespective of its environment. And ultimately that's what causes leukemia and cancer.

In normal cells when they have mutations, what ends up happening is that the cells self-destruct. So we get cells that have mutations all the time. You know, you have cells dividing all the time, all throughout your body. But a normal cell when it develops a mutation that is bad for the cell, it will sort of self-destruct. And then that mutation never causes a problem. In leukemia, when you get mutations in certain genes, for reasons that we don't completely understand, that cell is unable to go away, the cell is unable to self-destruct. And that's what leads to the development of the disease.