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WHO 2022 AML Classification Mapper

WHO 2022 Updates: Genetic abnormalities now take precedence over blast percentage. AML with mutations like NPM1 or t(8;21) can be diagnosed even if blasts are < 20%.

Select genetic finding to categorize

Guidelines & Evidence

Clinical Details

Section 1

When to Use

Classifying newly diagnosed Acute Myeloid Leukemia (AML) according to the 5th edition of the WHO Classification of Haematolymphoid Tumours.

Integrating cytogenetic and molecular findings with morphological assessment.

Identifying specific "Defined Genetic Abnormalities" that now override the 20% blast threshold.

2022 Revision Key

The 2022 WHO update emphasizes the elimination of the mandatory 20% blast threshold for AML with defining genetic abnormalities (with the exception of BCR::ABL1).

Section 2

Formula & Logic

AML with Defined Genetic Abnormalities

Subtype	Defining Genetic Feature	Notes
AML with promyelocytic (APL)	PML::RARA	Blast threshold not required.
AML with NPM1 mutation	NPM1	Blast threshold not required.
AML with CEBPA mutation	in-frame bZIP mutation	Previously "biallelic," now bZIP-specific.
AML with KMT2A rearrangement	t(11q23.3)	Formerly MLL; blast threshold not required.
AML with RUNX1::RUNX1T1	t(8;21)	Classic favorable risk; threshold not required.
AML with CBFB::MYH11	inv(16) or t(16;16)	Classic favorable risk; threshold not required.

AML, Myelodysplasia-related (AML-MR)

Now defined by specific cytogenetic abnormalities or somatic mutations in genes such as ASXL1, BCOR, SF3B1, SRSF2, STAG2, U2AF1, or ZRSR2. Morphological dysplasia alone is no longer sufficient for this category.

Section 3

Pearls/Pitfalls

The 10% Grey Zone

Patients with 10–19% myeloblasts and defining genetic abnormalities (like t(8;21)) are now formally classified as having AML, rather than Myelodysplastic Syndrome (MDS-EB-2).

Therapeutic Pivot

Molecular classification is the primary driver for targeted therapy selection (e.g., FLT3 inhibitors, IDH1/2 inhibitors, or CPX-351 for AML-MR).

Section 4

Evidence Appraisal

Primary Strategy

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms.

Khoury JD et al. • Leukemia. 2022;36(7):1703-1719.

View Source

Comparison of the WHO 2022 and ICC 2022 classifications of AML.

Daver N et al. • Blood Reviews. 2023;Analysis of concordances and differences.

View Source

Section 5

Literature

Nomenclature

Developed through an international consensus of hematopathologists and clinicians to replace the 2016 4th Revised Edition.

Last Comprehensive Review: 2026

Guidelines & Evidence

Clinical Details

Section 1

When to Use

Classifying newly diagnosed Acute Myeloid Leukemia (AML) according to the 5th edition of the WHO Classification of Haematolymphoid Tumours.

Integrating cytogenetic and molecular findings with morphological assessment.

Identifying specific "Defined Genetic Abnormalities" that now override the 20% blast threshold.

2022 Revision Key

The 2022 WHO update emphasizes the elimination of the mandatory 20% blast threshold for AML with defining genetic abnormalities (with the exception of BCR::ABL1).

Section 2

Formula & Logic

AML with Defined Genetic Abnormalities

Subtype	Defining Genetic Feature	Notes
AML with promyelocytic (APL)	PML::RARA	Blast threshold not required.
AML with NPM1 mutation	NPM1	Blast threshold not required.
AML with CEBPA mutation	in-frame bZIP mutation	Previously "biallelic," now bZIP-specific.
AML with KMT2A rearrangement	t(11q23.3)	Formerly MLL; blast threshold not required.
AML with RUNX1::RUNX1T1	t(8;21)	Classic favorable risk; threshold not required.
AML with CBFB::MYH11	inv(16) or t(16;16)	Classic favorable risk; threshold not required.

AML, Myelodysplasia-related (AML-MR)

Section 3

Pearls/Pitfalls

The 10% Grey Zone

Patients with 10–19% myeloblasts and defining genetic abnormalities (like t(8;21)) are now formally classified as having AML, rather than Myelodysplastic Syndrome (MDS-EB-2).

Therapeutic Pivot

Molecular classification is the primary driver for targeted therapy selection (e.g., FLT3 inhibitors, IDH1/2 inhibitors, or CPX-351 for AML-MR).

Section 4

Evidence Appraisal

Primary Strategy

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms.

Khoury JD et al. • Leukemia. 2022;36(7):1703-1719.

View Source

Comparison of the WHO 2022 and ICC 2022 classifications of AML.

Daver N et al. • Blood Reviews. 2023;Analysis of concordances and differences.

View Source

Section 5

Literature

Nomenclature

Developed through an international consensus of hematopathologists and clinicians to replace the 2016 4th Revised Edition.

Last Comprehensive Review: 2026

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IPSS-R

IPSS-M

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WHO 2022 AML Classification Mapper

WHO 2022 Updates: Genetic abnormalities now take precedence over blast percentage. AML with mutations like NPM1 or t(8;21) can be diagnosed even if blasts are < 20%.

Select genetic finding to categorize

Guidelines & Evidence

Clinical Details

Section 1

When to Use

Classifying newly diagnosed Acute Myeloid Leukemia (AML) according to the 5th edition of the WHO Classification of Haematolymphoid Tumours.

Integrating cytogenetic and molecular findings with morphological assessment.

Identifying specific "Defined Genetic Abnormalities" that now override the 20% blast threshold.

2022 Revision Key

The 2022 WHO update emphasizes the elimination of the mandatory 20% blast threshold for AML with defining genetic abnormalities (with the exception of BCR::ABL1).

Section 2

Formula & Logic

AML with Defined Genetic Abnormalities

Subtype	Defining Genetic Feature	Notes
AML with promyelocytic (APL)	PML::RARA	Blast threshold not required.
AML with NPM1 mutation	NPM1	Blast threshold not required.
AML with CEBPA mutation	in-frame bZIP mutation	Previously "biallelic," now bZIP-specific.
AML with KMT2A rearrangement	t(11q23.3)	Formerly MLL; blast threshold not required.
AML with RUNX1::RUNX1T1	t(8;21)	Classic favorable risk; threshold not required.
AML with CBFB::MYH11	inv(16) or t(16;16)	Classic favorable risk; threshold not required.

AML, Myelodysplasia-related (AML-MR)

Section 3

Pearls/Pitfalls

The 10% Grey Zone

Patients with 10–19% myeloblasts and defining genetic abnormalities (like t(8;21)) are now formally classified as having AML, rather than Myelodysplastic Syndrome (MDS-EB-2).

Therapeutic Pivot

Molecular classification is the primary driver for targeted therapy selection (e.g., FLT3 inhibitors, IDH1/2 inhibitors, or CPX-351 for AML-MR).

Section 4

Evidence Appraisal

Primary Strategy

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms.

Khoury JD et al. • Leukemia. 2022;36(7):1703-1719.

View Source

Comparison of the WHO 2022 and ICC 2022 classifications of AML.

Daver N et al. • Blood Reviews. 2023;Analysis of concordances and differences.

View Source

Section 5

Literature

Nomenclature

Developed through an international consensus of hematopathologists and clinicians to replace the 2016 4th Revised Edition.

Last Comprehensive Review: 2026

Guidelines & Evidence

Clinical Details

Section 1

When to Use

Classifying newly diagnosed Acute Myeloid Leukemia (AML) according to the 5th edition of the WHO Classification of Haematolymphoid Tumours.

Integrating cytogenetic and molecular findings with morphological assessment.

Identifying specific "Defined Genetic Abnormalities" that now override the 20% blast threshold.

2022 Revision Key

The 2022 WHO update emphasizes the elimination of the mandatory 20% blast threshold for AML with defining genetic abnormalities (with the exception of BCR::ABL1).

Section 2

Formula & Logic

AML with Defined Genetic Abnormalities

Subtype	Defining Genetic Feature	Notes
AML with promyelocytic (APL)	PML::RARA	Blast threshold not required.
AML with NPM1 mutation	NPM1	Blast threshold not required.
AML with CEBPA mutation	in-frame bZIP mutation	Previously "biallelic," now bZIP-specific.
AML with KMT2A rearrangement	t(11q23.3)	Formerly MLL; blast threshold not required.
AML with RUNX1::RUNX1T1	t(8;21)	Classic favorable risk; threshold not required.
AML with CBFB::MYH11	inv(16) or t(16;16)	Classic favorable risk; threshold not required.

AML, Myelodysplasia-related (AML-MR)

Section 3

Pearls/Pitfalls

The 10% Grey Zone

Patients with 10–19% myeloblasts and defining genetic abnormalities (like t(8;21)) are now formally classified as having AML, rather than Myelodysplastic Syndrome (MDS-EB-2).