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Acute Myelogenous Leukemia (AML) not otherwise categorized - General Information

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Definition

Acute myelogenous leukemia (AML) is a clonal expansion of the myeloid blasts in bone marrow, blood or other tissues.

Epidemiology

The incidence of acute leukemia is approximately 4 cases per 100,000 per year. 70% of these are AML. AML is generally seen in adults  with a median age of 60 years. In this age group the incidence is 10 cases per 100,000. There are approximately 9700 cases of AML in the United States per year. The male female ratio for AML is 1:1.

Subclassification and frequency  of AML
Subclassification Frequency

Acute nonlymphocytic (ANLL)

 

M1 Myeloblastic (AML)

10-20%

M2 AML with differentiation

30-40%

M3 Promyelocytic (APL)

10-15%

M4 Myelomonocytic(AMML, Naegeli)

10-15%

M5a Monoblastic (AMoL, Schilling)

10-15%

M5b AMoL with differentiation

<5%

M6 Erythroleukemia (Di Guglielmo)

<5%

M7 Megakaryoblastic

<5%

Other (e.g. biphenotypic)

<5%
Possible causes

Similar to all, possible factors that have been associated with AML (and MDS) are viruses, radiation, cytotoxic chemotherapy and benzene exposure. Exposure to the atomic bomb of WWII increased the incidence of all leukemias including AML. In addition, smoking is attributed to an increased risk.

Morphology

Myeloblasts vary in size from slightly larger than lymphocytes to larger than a monocyte. These blasts have abundant basophillic cytoplasm.  The nucleoi are round with fine chromatin and multiple nucleoli. Some azurophillc granules or Auer rods are present in the cytoplasm.

Below are example morphology of selected AML types:

Example morphology of AML-M0 Example morphology of AML-M1 Example morphology of AML-M2
 Example morphology of AML-M3 (hypercellular)  Example morphology of AML-M5 Example morphology of AML-M6
Sub-classification of AML

The WHO classification for AML is:

1. Acute myeloid leukemia with recurrent genetic abnormalities

2. Acute myeloid leukemia with multilineage dysplasia

3. Acute myeloid leukemia and myelodysplastic syndrome, therapy related

4. Acute myeloid leukemia not otherwise categorized

(flow cytometric immunophenotyping is helpful in diagnosis and/or classification) *

The 2006 International Bethesda Consensus recommends the following CD markers for the initial evaluation of myeloid leukemias:

CD7, CD11b, CD13, CD14, CD15, CD16, CD33, CD34, CD45, CD56, CD117, HLA Dr.

Additional CD Markers for secondary evaluation of myeloid lineage are:

CD2, cCD3, CD4, cCD22, CD25, CD36, CD38, CD41, CD61, cCD61, CD64, CD71, cCD79a, cMPO, CD123, CD163, CD235a.

   

Immunophenotyping

The following is a table that indicates the specific immunophenotypic markers and their reactions for each type of AML:

Marker AML-M0 AML-M1 AML-M3 (APL) AML-M4 (blasts) AML-M4 (monos) AML-M5 AML-M6 AML-M7
CD2   -   -   +/-   -   -   -   -   -
CD3   -   -   -   -   -   -   -   -
CD4   +/-   +/-   +/-   +/-   +   +   -   -/+
CD7   -/+   -/+   -/+   -/+   +/-   +/-   -   -/+
CD10   -   -   -   -   -   -   -   -
CD11b   -   -   -   -   +   +   -   -
CD11c   -/+   -/+   -/+   +/-   +   +   -   -
CD13   +   +   +   +   +   dim+   -   -/dim+
CD14   -   -   -   -   +   +/-   -   -
CD16   -   -   -   -   -   -/+   -   -
CD19   -   +   -   -   -   -   -   -
CD20   -   -   -   -   -   -   -   -
CD22   -   -   -   -   -   -   -   -
CD33   +   +   +   +   +   bright+   -   bright+
CD34   +   +   -   +   -   +/-   +/-   -/rare+
CD41   -   -   -   -   -   -   -   +
CD45   +   +   +   +   +   +   -/rare+   +/rare-
CD56   -/+   +/rare-   -/+   -   -/+   +/-   -/rare+   -/rare+
CD61   -   -   -   -   -   -   -   +
CD64   -/+   -/+   -/+   -/+   +   +/-   -   -
CD79a   -   -   -   -   -   -   -   -
CD117   +   +   +   +   -   -/+   dim+   dim+
HLA-DR   +/rare-   +/rare-   -   +   +   +/-   +   -/dim
TdT   -/+   -/+   -   -   -   -   -   -
GPHA   -   -   -   -   -   -   +   -
cIgM   -   -   -   -   -   -   -   -
Flow Diagnosis

To diagnose, please see the specific AML type below