AML

A c u t e M y e l o i d L e u k e m i a

Definition

AML is a malignant proliferation of myeloblasts (or related cells) in the bone marrow and blood. The myeloblasts (or related cells) must comprise at least 20% of all the nucleated cells in the blood and/or bone marrow to make the diagnosis of AML (if only 10% of all the nucleated cells are blasts, for example, then you can’t call it AML).

Classification

There are lots of different kinds of AML. Some have unique genetic abnormalities. Some have monoblasts, or erythroblasts, or something else instead of myeloblasts. All of these different types have to be classified in some way that makes sense for therapy and prognosis.

Right now, we’re in between two different classifications. The old one (called the FAB, or French-American-British classification; labels AML as M0, M1, M2 etc.) was based mostly on morphology (how the cells look). The new one (created by the World Health Organization) takes into account a lot of different things, such as morphology, genetic changes, and whether the leukemia is related to previous chemotherapy. It is more helpful for determining treatment and prognosis. Here's a good article that tells a lot about this classification.

There is also a separate, but related, category of diseases known as myelodysplastic syndromes (or MDS). These are disorders of myeloid cells in which there is myelodysplasia (and sometimes an increase in blasts - but never more than 20%!). Some cases of MDS evolve into acute myeloid leukemia. You should know a bit about these, so take a look at the MDS page.

WHO classification (with FAB types listed too)

1. AML with genetic abnormalities

• t(8;21)

• inv(16)

• t(15;17)

• 11q23

2. AML with an FLT3 mutation

3. AML with multilineage dysplasia

4. AML and MDS, therapy related

5. AML not otherwise cateorized

• M0 - Acute myeloblastic leukemia, minimally differentiated

• M1 - Acute myeloblastic leukemia without maturation

• M2 - Acute myeloblastic leukemia with maturation

• M4 - Acute myelomonocytic leukemia

• M5 - Acute monocytic leukemia

• M6 - Acute erythroid leukemia

• M7 - Acute megakaryoblastic leukemia

How to Make a Diagnosis

Morphology (Wright-Giemsa)

• Basic requirement for diagnosis

• At least 20% of all nucleated cells in the blood or marrow must be

myeloblasts.

• In M3, M4, M5, and M7, the predominating cell type (see below) is

considered to be equivalent to the myeloblast in order to fulfill the 20%

criteria.

• Individual cell morphology

• Myeloblast: Large nucleus with fine chromatin, nucleoli. Thin rim of

basophilic cytoplasm. May have a few fine, azurophilic, cytoplasmic

granules.

• Promyelocyte: Biggest cell in myeloid line. Lots of primary (coarse,

azurophilic) granules.

• Monoblast: Typical blast cell but larger, with more oval-shaped nucleus.

• Promonocyte: Delicate "tissue-paper" folds in nucleus.

• Monocyte: Large cell with grayish ("dishwater") cytoplasm, "raked"

chromatin.

• Other clues to myeloid nature

• Dysgranulopoiesis: Disordered granulocyte production

(e.g., hypogranularity or hyposegmentation).

• Auer rods: Consolidation of azurophilic granules. If present, Auer rods

prove myeloid lineage!

Cytochemical stains

• Myeloperoxidase (MPO) - + in neutrophils and eosinophils.

• Sudan black B (SBB) - same pattern as MPO.

• Non-specific esterase (NSE) - + in monocytic lineage.

Immunophenotyping

• Use when morphologic and cytochemical features are equivocal.

• Commonly-used markers include:

• General "pan-myeloid" markers such as CD33.

• Specific markers such as CD61 (for platelets).

Cytogenetics/Molecular Studies

• Several subtypes of AML have specific chromosomal abnormalities

(compared to other types of AML, these subtypes are treated differently,

and have different prognosis).

• These are the most important abnormalities:

• t(8;21) (better prognosis)

• t(15;17) (better prognosis)

• inv(16) (better prognosis)

• 11q23 (worse prognosis)

• AML with FLT3 mutation (worse prognosis)

Treatment and Prognosis

Treatment

• Chemotherapy (often get complete remission; unfortunately,

often short lived).

• Bone marrow transplantation (better chance for cure).

Prognosis

• About 2/3 of patients achieve complete remission after initial therapy

• However, 80% of patients die within 3 years.

• Prognosis varies inversely with age (older patients do worse)

• Prognosis also varies depending on the presence of chromosomal

abnormalities:

• Patients with t(8;21), inv (16), and especially t(15;17) survive longer.

• Patients with FLT-3 mutations or 11q23 abnormalities have a worse

prognosis.