Acute leukemia

With acute leukemia, leuk- refers to white blood cells, and -emia refers to the blood, so in acute leukemia, there’s uncontrolled proliferation of partially developed white blood cells, also called blast cells, which build up in the blood over a short period of time.

Although leukemia means cancer white blood cells, it can also be used to refer to cancer of any of the blood cells, including red blood cells and platelets.

Acute leukemia can be broadly classified into acute myeloid leukemia, or AML; and acute lymphoblastic leukemia, ALL.

AML is more common in old age, where as ALL is more common in children. In both cases, accumulation of blast cells interferes with the development and function of healthy white blood cells, platelets, and red blood cells.

Now, every blood cell starts its life in the bone marrow as a hematopoietic stem cell. Hematopoietic stem cells are multipotent -- meaning that they can give rise to both myeloblasts, which are precursors of myeloid blood cells, and lymphoblasts, which are precursors of lymphoid blood cells.

These lymphoblasts can be pre-B cells, which develop into B lymphocytes; or pre-T cells, which develop into T lymphocytes.

If a hematopoietic stem cell develops into a myeloid cell, it’ll mature into an erythrocyte -- or a red blood cell, a thrombocyte -- or a platelet, or a leukocyte -- or a white blood cell, like a monocyte or granulocyte.

Granulocytes are cells with tiny granules inside of them -- they include neutrophils, basophils, and eosinophils.

If a hematopoietic stem cell develops into a lymphoid cell, on the other hand, it’ll mature into some other kind of leukocyte: a T cell, a B cell, or a natural killer cell, which are referred to as lymphocytes.

Once the various blood cells form, they leave the bone marrow, and travel around the blood, or settle down in tissues and organs like the lymph nodes and spleen.

Acute leukemia is caused by a mutation in the precursor blood cells in the bone marrow. In the case of ALL it’s usually due to a chromosomal translocation or due to an abnormal chromosome number.

Common chromosomal translocations include translocation of chromosome 12 and 21 and translocation of chromosome 9 and 22, also called the Philadelphia chromosome.

These result in production of abnormal intracellular proteins, which affect the cell’s function and cell division.

ALL can further be classified into T-cell ALL, where there’s proliferation of T-cell precursors, and B-cell ALL, where there’s proliferation of B-cell precursors.

AML is caused by a wide variety of abnormalities like chromosomal translocations, which are used to subclassify AML into a few different types.

AML can also be classified based on the morphology of the myeloblast into AML without maturation; AML with minimal maturation, AML with maturation; acute promyelocytic leukemia; acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia.

Of these, acute promyelocytic leukemia is an important subtype. It is characterized by translocation of chromosome 15 and 17 which disrupts the retinoic acid receptor alpha gene, which is required for normal cell division.

Now, there are also certain conditions that can actually lead to AML, like myelodysplastic syndrome, which is characterized by defective maturation of myeloid cells and buildup of blasts in the bone marrow.

Usually the buildup is initially less than 20% blasts. But that’s enough to cause a decrease in the function of red blood cells, granulocytes, and platelets.

As the disease progresses, the blast percentage may go over 20%, resulting in AML with a background of myelodysplasia.

Another condition often associated with both AML and ALL is Down syndrome, which is caused by an extra 21st chromosome - so that there’s a trisomy 21.

Finally, there are also some risk factors for acute leukemia like exposure to radiation, and alkylating chemotherapy, which may have been used as treatment of some other type of cancer.

Alright, now regardless of the type of mutation, acute leukemias share a similar pathogenesis. The mutation does two things.

First, it causes these precursor blood cells to lose their ability to differentiate into mature blood cells.

This means that they’re stuck in the blast stage of development, and the blast cells don’t function effectively.

Second, it makes the blast cells divide uncontrollably, and in the process take up a lot of space and nutrition in the bone marrow.