Subtypes of Acute Myeloid Leukemia

Executive Summary

Specific chromosomal or genetic changes in the cancer cells help plan treatment and also to predict the prognosis. There are various subtypes of acute myeloid leukemia such as myeloid leukemia, monocytic or monoblastic leukemia, and acute promyelocytic leukemia. The classification system formed by the World Health Organization (WHO) includes groups such as AML with recurrent genetic abnormalities, meaning specific chromosomal changes, and AML with multilineage dysplasia, or abnormalities in how the blood cells appear, to name a few.

The French-American-British classification is an older system for describing AML that includes classification as M0, M1, M2, M3, M4, M4eo, M5a, M5b, M6, and M7.AML is also classified by the cytogenetic or chromosomal changes in leukemia cells involving genetic changes such as translocation, deletion of a chromosome, and extra copies. Some of the most common chromosomal changes include favourable, intermediate, and unfavorable. In addition to it, there are other genetic modifications with the prognosis for people with AML include RUNX1, IDH1 and IDH2, ASX11, and P53. 

Subtypes of Acute Myeloid Leukemia

Furthermore, there are various ways to classify the subtypes of Acute myeloid leukemia. Although all subtypes lead to decreases in normal blood cell levels, different types of AML are has specific problems and symptoms. Additionally, each subtype can behave differently after the treatment. 

Morphology

The morphology describes the AML, or what the cancerous cells look like under the microscope. The morphology describes the AML. The AML is further classified by the normal, immature white blood cell it most closely resembles.  

Most people having AML have a subtype called myeloid leukemia, which means the cancer is in the cells that usually produce neutrophils. Whereas, other patients have a type of AML called monocytic or monoblastic leukemia. In monocytic leukemia, the cells look like white blood cells called monocytes. Leukemia cells can also be a mixture of myeloblastic and monocytic cells.

Sometimes AML comes from cells that produce red blood cells, called erythroid or megakaryocytic platelets.

Acute promyelocytic leukemia is a subtype of AML where the cancer cell stops maturing. And when the cell is at a stage, the progranulocyte or promyelocyte stage. Acute Promyelocytic Leukemia is associated with a translocation between chromosomes 15 and 17 [t(15;17)].

The classification system formed by the World Health Organization (WHO) includes these significant groups ^​1​:

• AML with recurrent genetic abnormalities, meaning with certain chromosomal changes
• The AML with multilineage dysplasia, or abnormalities in how the blood cells appear
• AML related therapy that is damaging to cells is the therapy-related myeloid neoplasm
• AML that is not otherwise categorized
• Myeloid sarcoma
• Myeloid proliferations related to Down Syndrome
• Undifferentiated or biphenotypic acute leukemias

The French-American-British classification is an old system for describing AML, but it is still in use and will benefit for reference. 

• M0- Myeloblastic without differentiation
• M1- Myeloblastic with little or no maturation
• M2-  Myeloblastic with maturation
• M3- Promyelocytic
• M4-  Myelomonocytic
• M4eo- Myelomonocytic with eosinophils
• M5a-  Monocytic without differentiation (monoblastic) 
• M5b-  Monocytic with differentiation
• M6-  Erythroleukemic
• M7-  Megakaryocytic

Cytogenetics

AML is also classified by the cytogenetic or chromosomal changes in leukemia cells. Specific chromosomal changes are closely matched with the morphology of the AML cells. More importantly, chromosomal changes help doctors find out the best treatment options because these changes can help predict how well intensive treatment will work. Chromosomal changes are usually grouped according to the likelihood that treatment will work against the subtype of acute myeloid leukemia. All chromosomes are marked from 1 to 22. And sex chromosomes are known as ‘X’ or ‘Y.’

The letters ‘p’, and ‘q’ signifies the arms or specific areas of the chromosome. Therefore, some of the types of genetic changes seen in AML include-

• A translocation, meaning that a chromosome breaks off and reattaches to other chromosomes
• Deletion of a chromosome
• Extra copies of a chromosome

Some of the most common chromosomal changes are mentioned ^​2​–

Favourable

Chromosomal changes linked with more successful treatment include abnormalities of chromosome 16 at bands p13 and q22 [t(16;16)(p13;q22), inv(16)(p13q22)] and a translocation between chromosomes 8 and 21 [t(8;21)].

Intermediate

However, the changes in the less favorable prognosis include normal chromosomes, where no modifications are found, and a translocation between chromosomes 9 and 11 [t(9;11)]. Many other subtypes are part of this group, particularly those with one or more specific molecular changes. Sometimes, extra copies of chromosome 8(trisomy eight) may be classified as an intermediate risk over unfavorable.

Unfavorable

Examples of chromosomal changes that are linked with less successful treatment or low scope of curing the AML include an extra copy of chromosome 8 or 13. For instance, trisomy 8 (+8), complex changes on many chromosomes, deletion of all or a part of chromosomes 5 or 7, and changes to chromosome 3 at band q26.

Generally, favorable changes occur more commonly in younger patients, while unfavorable changes are more common in people older than 60. How well the treatment works still varies widely in each of the groups. Treatment is successful in the long run for 50% to 60% of patients younger than 60 having AML classified as favorable. And for less than 10% of patients younger than 60 with AML classified as unfavorable. Prognosis in patients older than age 60 is significantly worse. How well the treatment works also depends on other factors, including white blood cells. And so, it is impossible to foresee the likelihood of successful treatment for a person with AML.

Molecular changes

Molecular changes testing at diagnosis helps determine a patient’s treatment options. For instance, patients with changes in the NPM1 or CEBPalpha genes have a better long-term outcome, while chemotherapy doesn’t work as well for patients with changes in the FLT3 gene. Other genetic modifications associated with the prognosis for people with AML include ^​3​–

• RUNX1
• IDH1 and IDH2
• ASX11
• P53

Recurrent AML

Recurrent AML is cancer that has returned after treatment. If the AML returns, there will be another round of tests about the recurrence. These tests and scans are generally similar to those at the original diagnosis.

References