FAB & WHO ACUTE MYELOID LEUKEMIA

Very immature blasts, no obvious signs of myeloid differentiation under the

microscope.

M0-AML with Minimal Differentiation

Cytochemical stains:

o Negative for Myeloperoxidase (MPO)

o Negative for Sudan Black B (SBB)

M0-AML with Minimal Differentiation

Diagnosis requires:

o Immunophenotyping (e.g., CD13, CD33, CD34, HLA-DR)

M0-AML with Minimal Differentiation

Clinical significance:

Difficult to recognize morphologically; may resemble ALL if only morphology is used.

Represents a very early block in myeloid differentiation.

M0-AML with Minimal Differentiation

Description:

90% of non-erythroid cells in marrow are myeloblasts

Little to no maturation beyond the blast stage.

M1 - AML without Maturation

Cytochemical stains:

o Strongly positive for MPO and SBB

M1 - AML without Maturation

Auer rods: May be present

M1 - AML without Maturation

Immunophenotyping: CD13+, CD33+, CD117+

M1 - AML without Maturation

Clinical clue: Classic case of "blasts everywhere." Cytochemistry confirms myeloid origin.

M1 - AML without Maturation

Myeloblasts are still predominant but with evidence of maturation into promyelocytes, myelocytes, or neutrophils.

M2-AML with Maturation

30% myeloblasts >10% maturing granulocytes

M2-AML with Maturation

Auer rods: Frequently seen

M2-AML with Maturation

Cytochemical stains:

Positive for MPO and SBB

M2-AML with Maturation

Cytogenetics

t(8;21) commonly seen in __

Associated with a better prognosis

M2-AML with Maturation

Clinical clue:

Nuclei may appear indented (early maturation); CD13+, CD33+, CD34+, HLA-DR+

M2-AML with Maturation

M3 -Acute Promyelocytic Leukemia (APL) ALSO KNOW AS?

Hypergranular Variant

Description:

o Dominated by abnormal promyelocytes with heavy granulation.

o Since there are plenty of primary granules in __, then there is more presence of auer rods.

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

Cytochemical stains:

Positive for MPO, ANCAE and SBB

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

starts to appear in promyelocyte

Primary granules

Auer rods found in bundle are called ______________

FAGGOT CELLS

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

- starts to appear in the myelocytic stage

Secondary granules

Since the predominant cells are promyelocytes - wherein there are more granules, then the cells are GRANULAR - that's why M3 is also called as ____

primary

Hypergranular

Cytogeneticss

o t(15;17)- fusion of PML and RARA genes

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

Clinical significance:

High risk of DIC (Disseminated Intravascular procoagulants from lysed promyelocytes.

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

Relationship: The predominant cells are the promyelocytes and because they are

______ - then they immediately can be destroyed while still under development.

They release the contents of their granules upon ____, including their lysosomal

granules. The contents of the granules of the lysed promyelocytes will activate both

coagulation and the fibrinolysis abnormally it leads to ____

abnormal

lysis

DIC

Treatment:

o All-Trans Retinoic Acid (ATRA) -induces differentiation of promyelocytes

M3 -Acute Promyelocytic Leukemia (APL) / Hypergranular Variant

(ATRA)

All-Trans Retinoic Acid

is a medical emergency due to DIC risk, but it's curable with prompt therapy.

M3

M4 - Acute Myelomonocytic Leukemia ALSO KNOWN AS?

(Naegeli-type)

Description:

o Mixed proliferation of myeloblasts and monoblasts

o >20% monocytes or monocytic precursors in blood.

M4 - Acute Myelomonocytic Leukemia (Naegeli-type)

Cytochemical stains:

o Positive for non-specific esterase (e.g., a-naphthyl acetate or butyrate)

M4 - Acute Myelomonocytic Leukemia (Naegeli-type)

Cytogenetics:

o inv(16) or t(16;16) (in some cases, associated with better prognosis)

M4 - Acute Myelomonocytic Leukemia (Naegeli-type)

Clinical features:

o May have gingival hypertrophy, skin infiltration, or CNS involvement due to monocytic lineage

M4 - Acute Myelomonocytic Leukemia (Naegeli-type)

M5-Acute Monocytic Leukemia ALSO KNOWN AS?

(Schilling- type)

Description:

80% of marrow cells are from the monocytic lineage

M5-Acute Monocytic Leukemia (Schilling- type)

Cytochemical stains:

Strong positivity for non-specific esterase

M5-Acute Monocytic Leukemia (Schilling- type)

Subtypes:

___ More mature, INCREASE promonocytes/and monocytes

___ Poorly differentiated, INCREASE monoblasts

M5b:

M5a:

Cytogenetics:

t(9;11) in some cases

M5-Acute Monocytic Leukemia (Schilling- type)

Clinical features:

o Frequent tissue infiltration (skin, gums, CNS)

o Gingival swelling and hepatosplenomegaly common

M5-Acute Monocytic Leukemia (Schilling- type)

o Erythroid/myeloid type,≥50% erythroid precursors + ≥20% myeloblasts

o Pure Erythroid Leukemia: Almost all abnormal erythroid precursors

M6-Acute Erythroid Leukemia (Di Guglielmo syndrome)

Cytochemical stains:

o PAS (Periodic Acid-Schiff) Positive in abnormal erythroblasts

Normal erythroblasts are PAS-negative, so a positive monocytic NPAS reaction indicates ____

M6-Acute Erythroid Leukemia (Di Guglielmo syndrome)

dysplasia.

Clinical notes:

May present with severe anemia and bizarre, vacuolated erythroid precursors

M6-Acute Erythroid Leukemia (Di Guglielmo syndrome)

Description:

o >30% of blasts are from megakaryocytic lineage

o Includes megakaryoblasts and micromegakaryocytes

M7 - Acute Megakaryocytic Leukemia

Diagnosis:

o Requires platelet-specific markers (CD41, CD42, CD61) via immunophenotyping

Morphology may be misleading due to variable blast size

M7 - Acute Megakaryocytic Leukemia

Cytochemical stains:

o Often negative or variable; nonspecific esterase may be weak

M7 - Acute Megakaryocytic Leukemia

Clinical association:

o Often seen in children with Down syndrome (especially under age 3)

M7 - Acute Megakaryocytic Leukemia

Bone marrow: Often fibrotic, requiring a core biopsy

M7 - Acute Megakaryocytic Leukemia

FOUR MAJOR CATEGORIES OF AML UNDER THE WHO CLASSIFICATION:

1. AML with Recurrent Cytogenetic Abnormalities

2. AML with Multilineage Dysplasia

3. AML, Therapy Related

4. AML, Not Otherwise Classified (AML,NOS)

This group includes AML subtypes with well-defined chromosomal translocations or inversions that are strongly associated with distinct clinical and morphologic features. These abnormalities are often diagnostic and have prognostic value.

AML with Recurrent Cytogenetic Abnormalities

often associated with AML-M2

t(8;21)

linked to AML-M4 with eosinophilia

inv(16) or t(16;16)

defines Acute Promyelocytic Leukemia (AML-M3)

t(15;17))

exchange of genetic material between two chromosomes

Translocation (t):

a segment of a chromosome is flipped in orientation

Inversion (inv):

Clinical Relevance:

These subtypes often have predictable responses to therapy.

For example, APL with t(15;17) responds dramatically to ATRA (All-Trans Retinoic Acid).

AML with Recurrent Cytogenetic Abnormalities

this category, AML arises in a background of pre-existing myelodysplasia or shows dysplasia more than one hematopoietic cell line (e.g., erythroid, granulocytic, and/or megakaryocytic series).

AML with Multilineage Dysplasia

Key Features:

Multilineage dysplasia must involve at least 50% of two or more cell lines in the bone marrow.

Can be de novo or evolve from a prior Myelodysplastic Syndrome (MDS).

AML with Multilineage Dysplasia

Clinical Significance:

Generally associated with a poorer prognosis

May have complex karyotypes and resistance to conventional chemotherapy.

AML with Multilineage Dysplasia

This type of AML develops as a direct consequence of previous cytotoxic chemotherapy or radiation therapy used to treat a different malignancy or condition.

AML, Therapy-Related

AML, Therapy-Related

AML, Therapy-Related

Radiation exposure:

Often leads to AML after a ___________ latency period

5-10 year

Alkylating agents:

Chlorambucil - Common

Cyclophosphamide

Busulfan

Thiotepa

Clinical Pathway:

Patients typically develop MDS first, a pre-leukemic stage, which then progresses into therapy- related AML

AML, Therapy-Related

Prognosis:

Therapy-related AML is often aggressive and resistant to treatment.

Frequently associated with poor cytogenetic profiles, including monosomies and complex karyotypes.

AML, Therapy-Related

AML, Therapy-Related

Frequently associated with poor cytogenetic profiles, including _______________ and ______________

monosomies and complex karyotypes

This is a catch-all category for cases that do not meet the criteria for the other three major groups. This category uses the traditional FAB subtypes (M0-M7) to further classify AML by morphologic and cytochemical features.

AML, Not Otherwise Classified (AML, NOS)