Subtypes of Acute Myeloid Leukemia

Executive Summary

Specific chromosomal or genetic changes in the cancer cells help plan treatment and predict prognosis. The subtypes of acute myeloid leukaemia include myeloid leukaemia, monocytic or monoblastic leukaemia, and acute promyelocytic leukaemia. The classification system formed by the World Health Organization (WHO) includes groups such as AML with recurrent genetic abnormalities, meaning with specific chromosomal changes, AML with multilineage dysplasia, or abnormalities in how the blood cells appear, AML related therapy that is damaging to cells is also called a therapy-related myeloid neoplasm, AML that is not otherwise categorized, myeloid sarcoma, myeloid proliferation associated with Down Syndrome, and undifferentiated or biphenotypic acute leukaemias. 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 leukaemia 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 unfavourable. Other genetic modifications associated with the prognosis for people with AML include RUNX1, IDH1 and IDH2, ASX11, and P53. 

Subtypes of Acute Myeloid Leukemia

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

Morphology

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

Most people having AML have a subtype called myeloid leukaemia, which means the cancer is in the cells that usually produce neutrophils. Other patients have a type of AML called monocytic or monoblastic leukaemia. In monocytic leukaemia, the cells look like white blood cells called monocytes. Leukaemia 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 leukaemia is a subtype of AML where the cancer cell stops maturing when the cell is at a stage known as the progranulocyte or promyelocyte stage. Acute Promyelocytic Leukaemia 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
  • AML with multilineage dysplasia, or abnormalities in how the blood cells appear
  • AML related therapy that is damaging to cells is also called a therapy-related myeloid neoplasm
  • AML that is not otherwise categorized
  • Myeloid sarcoma
  • Myeloid proliferations related to Down Syndrome
  • Undifferentiated or biphenotypic acute leukaemias

The French-American-British classification is an older system for describing AML, but it is still commonly used and is listed below 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 leukaemia 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 leukaemia.

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. 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 – Changes associated with a less favourable prognosis include normal chromosomes, where no modifications are found and a translocation between chromosomes 9 and 11 [t(9;11)]. Many other subtypes are considered 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 unfavourable.
  • Unfavourable – 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 example, 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, favourable changes occur more commonly in younger patients, while unfavourable 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 favourable, and for less than 10% of patients younger than 60 with AML classified as unfavourable. Prognosis in patients older than age 60 is significantly worse. How well the treatment works also depends on other factors, including white blood cells. 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 usually similar to those at the original diagnosis.

References

  1. 1.
    Hwang SM. Classification of acute myeloid leukemia. Blood Res. Published online July 31, 2020:S1-S4. doi:10.5045/br.2020.s001
  2. 2.
    Schlenk RF, Taskesen E, van Norden Y, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. Published online August 29, 2013:1576-1582. doi:10.1182/blood-2013-05-503847
  3. 3.
    Dufour A, Schneider F, Metzeler KH, et al. Acute Myeloid Leukemia With Biallelic CEBPA Gene Mutations and Normal Karyotype Represents a Distinct Genetic Entity Associated With a Favorable Clinical Outcome. JCO. Published online February 1, 2010:570-577. doi:10.1200/jco.2008.21.6010