There’s an 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, whereas ALLis are more common in children.
In both cases, the 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 — ora platelet, or a leukocyte — or a white blood cell, like a monocyte of 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 the production of abnormal intracellular proteins, which affect the cell’s function and cell division. ALL can further be classified into T-cellALL, where there’s the proliferation of T-cell precursors, and B-cell ALL, where there’sproliferation 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 chromosome15 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 than20% 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 AMD and ALL is Down syndrome, which is caused by an extra 21st chromosome – so that there’s 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 a treatment of some other type of cancer. Alright, now regardless of the type of mutation, acute leukemias share 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 last 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.
This means that the other normal blood cells growing in the bone marrow get “crowded out”, and it’s tough for them to survive with the extra competition for nutrients. This causes cytopenias, or a reduction in the number of healthy blood cells, like anemia, which is a reduction of healthy red blood cells, thrombocytopenia, a reduction of healthy platelets, and leukopenia, or a reduction of healthy leukocytes. As the number of blast cells in the bone marrow keeps increasing, they spill out into the blood.
Now some of these guys, especially lymphoblasts, settle down in organs and tissues across the body, like the liver and spleen. Sometimes, pre- T cells, in T- cell ALL migrate to the thymus or lymph nodes like normal T-cells do, and settle down there, causing these structures to enlarge. Also, in acute promyelocytic leukemia, the promyelocytes activate the clotting process, and this combined with the already decreased platelets, results in disseminated intravascular coagulation.
Symptoms of both AML and ALL include fatigue, because of the anemia, easier bleeding, because of the thrombocytopenia, and more frequent infections, because of the leukopenia. Pain and tenderness in the bones can occur when there’s increased cell production which causes the bone marrow to expand. Hepatosplenomegaly often causes a feeling of abdominal fullness, while lymphadenopathy often causes mild, but localized pain in the lymph nodes.
However, hepatosplenomegaly and lymphadenopathy both seem more prominent in ALL than in AML. In addition, the monocytic variety of AML causes swelling of gums because of monocytic infiltration. Thymus enlargement in T-ALL may present as a mass, or growth in the mediastinum. The diagnosis of AML and ALL usually starts with a peripheral blood smear, which shows a lot of blast cells, myeloblasts in the case of AML, and lymphoblasts in the case of ALL. This is usually followed up by a bone marrow biopsy, which also shows an increase in blast cells.
IN acute leukemia, the percentage of blast cells in the bone marrow goes up from their normal value of 1-2% to greater than 20%! An important step in the diagnosis is to differentiateAML from ALL. This can be done by identifying the blast cells as either myeloblast or lymphoblasts in a specially stained smear. Myeloblasts are usually large cells with nuclei containing fine chromatin and prominent nucleoli. A classic feature of myeloblasts in AML, especially acute promyelocytic leukemia, is the presence of Auer rods in the cytoplasm,
Which are crystallized aggregates of the myeloperoxidase enzyme. On the other hand, lymphoblasts are relatively smaller cells with coarse chromatin, which are clumped together and have small nucleoli. Lymphoblasts have very little cytoplasm, which has glycogen granules. In addition, immunophenotyping is done to detect certain markers, for example, TdT, which is a DNA polymerase that’s present only in the nucleus of the lymphoblast, is a marker for lymphoblasts, and CD10 is a surface marker for pre-B cells.
Treatment of acute leukemia is mainly aimed at reducing the number of blast cells, to allow the other blood cells to develop normally. Treatment of AML and ALL is based on the type and stage of cancer, but in general involves chemotherapy, biological therapy, stem cell transplants, or bone marrow transplants. Acute promyelocytic leukemia can be treated with all-trans-retinoic acid, or ATRA, which is a derivative of vitamin A. ATRA binds to the disrupted retinoic acid receptor and causes the blasts to mature into neutrophils, which eventually go on to die.