Blood Res (2024) 59:15

Published online April 15, 2024

https://doi.org/10.1007/s44313-024-00016-8

© The Korean Society of Hematology

What is new in acute myeloid leukemia classification?

Hee Sue Park1,2*

1Department of Laboratory Medicine, Chungbuk National University Hospital, 776, 1 Sunhwan‑ro, Seowon‑gu, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea
2Department of Laboratory Medicine, Chungbuk National University College of Medicine, 776, 1 Sunhwan‑ro, Seowon‑gu, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea

Correspondence to : *Hee Sue Park
hsmed22@chungbuk.ac.kr

Received: December 29, 2023; Accepted: April 5, 2024

Abstract

Recently, the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO2022) introduced diagnostically similar yet distinct approaches, which has resulted in practical confusion. This review compares these classification systems for acute myeloid leukemia (AML), building up on the revised 4th edition of WHO (WHO2016). Both classifications retain recurrent genetic abnormalities as a primary consideration. However, they differ in terms of blast threshold. The ICC mandates a minimum of 10% blasts in the bone marrow or peripheral blood, whereas the WHO2022 does not specify a blast cut-off. AML with BCR::ABL1 requires > 20% blast count in both classifications. In WHO2022, AML with CEBPA mutation requires > 20% blasts. TP53 mutation, a new entity is exclusive to ICC, diagnosed with > 20% blasts and variant allele frequency > 10%. AML with myelodysplasia-related changes is defined by cytogenetic or gene mutation-based criteria, not morphological dysplasia. Eight genes were common to both groups: ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. An additional gene, RUNX1, was included in the ICC classification. AML cases defined by differentiation (WHO2022) and AML not otherwise specified (ICC) are categorized as lacking specific defining genetic abnormalities, WHO2022 labels this as a myeloid neoplasm post cytotoxic therapy (MN-pCT), described as an appendix after specific diagnosis. Similarly, in ICC, it can be described as “therapy-related”, without a separate AML category.

Keywords Acute myeloid leukemia, International Consensus Classification, WHO classification

Article

REVIEW

Blood Res 2024; 59():

Published online April 15, 2024 https://doi.org/10.1007/s44313-024-00016-8

Copyright © The Korean Society of Hematology.

What is new in acute myeloid leukemia classification?

Hee Sue Park1,2*

1Department of Laboratory Medicine, Chungbuk National University Hospital, 776, 1 Sunhwan‑ro, Seowon‑gu, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea
2Department of Laboratory Medicine, Chungbuk National University College of Medicine, 776, 1 Sunhwan‑ro, Seowon‑gu, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea

Correspondence to:*Hee Sue Park
hsmed22@chungbuk.ac.kr

Received: December 29, 2023; Accepted: April 5, 2024

Abstract

Recently, the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO2022) introduced diagnostically similar yet distinct approaches, which has resulted in practical confusion. This review compares these classification systems for acute myeloid leukemia (AML), building up on the revised 4th edition of WHO (WHO2016). Both classifications retain recurrent genetic abnormalities as a primary consideration. However, they differ in terms of blast threshold. The ICC mandates a minimum of 10% blasts in the bone marrow or peripheral blood, whereas the WHO2022 does not specify a blast cut-off. AML with BCR::ABL1 requires > 20% blast count in both classifications. In WHO2022, AML with CEBPA mutation requires > 20% blasts. TP53 mutation, a new entity is exclusive to ICC, diagnosed with > 20% blasts and variant allele frequency > 10%. AML with myelodysplasia-related changes is defined by cytogenetic or gene mutation-based criteria, not morphological dysplasia. Eight genes were common to both groups: ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. An additional gene, RUNX1, was included in the ICC classification. AML cases defined by differentiation (WHO2022) and AML not otherwise specified (ICC) are categorized as lacking specific defining genetic abnormalities, WHO2022 labels this as a myeloid neoplasm post cytotoxic therapy (MN-pCT), described as an appendix after specific diagnosis. Similarly, in ICC, it can be described as “therapy-related”, without a separate AML category.

Keywords: Acute myeloid leukemia, International Consensus Classification, WHO classification

Table 1 . Classification of acute myeloid leukemia with recurrent genetic abnormalities.

WHO2016WHO2022ICC
ClassificationBlast (%)ClassificationBlast (%)ClassificationBlast (%)
AML with recurrent genetic abnormalitiesAML with defining genetic abnormalitiesAML with recurrent genetic abnormalities
APL with PML::RARA.APL with PML::RARA fusion.APL with t(15;17)(q24.1;q21.2)/PML::RARA APL with other RARA rearrangement≥ 10
AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1.AML with RUNX1::RUNX1T1 fusion.AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1≥ 10
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11.AML with CBFB::MYH11 fusion.AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11≥ 10
AML with t(9;11)(p21.3;q23.3);KMT2A::MLLT3≥ 20AML with KMT2A rearrangement.AML with t(9;11)(p21.3;q23.3)/MLLT3::KMT2A AML with other KMT2A rearrangement≥ 10
AML with t(6;9)(p23;q34.1);DEK::NUP14≥ 20AML with DEK::NUP214 fusion.AML with t(6;9)(p23;q34.1)/DEK::NUP14≥ 10
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2::MECOM≥ 20AML with MECOM rearrangement.

AML with inv(3)(q21.3q26.2) or t(3;3).

(q21.3;q26.2)/GATA2;MECOM(EVI1).

AML with other MECOM rearrangement.

≥ 10
AML with t(9;22)(q34.1;q11.2)/BCR::ABL1≥ 20AML with BCR::ABL1 fusion≥ 20AML with t(9;22)(22)(q34.1;q11.2)/BCR::ABL1≥ 20
AML with t(1;22)(p13.3;q13.1);RBM15::MLK1≥ 20AML with RBM15::MRTFA fusion.≥ 10
AML with mutated NPM1.AML with NPM1 mutationAML with mutated NPM1≥ 10
AML with biallelic mutation of CEBPA.AML with CEBPA mutation≥ 20AML with mutated bZIP CEBPA≥ 10
(provisional) AML with mutated RUNX1≥ 20AML with NUP98 rearrangement.AML with TP53≥ 20
AML myeloid leukemia, myelodysplasia-related≥ 20AML with other rare recurring translocations≥ 10
AML with other defined genetic alteration≥ 20AML with t(1;3)(p36.3;q21.3)/PRDM16::RPN1
AML with t(3;5)(q25.3)(q25.3;q35.1)/NPM1::MLF1
AML with t(8;16)(p11.2;p13.3)/KAT6A::CREBBP
AML with t(1;22)(p13.3;q13.1)/RBM15::MRTF1
AML with t(5;11)(q35.2;p15.4)/NUP98:NSD1
AML with t(11;12)(p15.4;p13.3)/NUP98::KMD5A
AML with NUP98 and other partners
AML with t(7;12)(q36.3;p13.2)/ETV6::MNX
AML with t(10;11)(p12.3);q14.2)/PICA LM::MLLT10
AML with t(16;21)(p11.2;q22.2)/FUS::ERG
AML with t(16;21)(q24.3;q22.1)/RUNX 1::CBFA2T3
AML with inv(16)(p13.3;q24.3)/CBFA 2T3::GLIS2

Table 2 . Classification of acute myeloid leukemia with myelodysplasia-related changes.

WHO2016WHO2022ICC
Complex karyotype (≥ 3 abnormalities)Cytogenetic abnormalitiesCytogenetic abnormalities
Unbalanced abnormalitiesComplex karyotype (≥ 3 abnormalities)Complex karyotype (≥ 3 abnormalities)
del(5q) or t(5q)5q deletion or loss of 5qdel(5q)/t(5q)/add(5q)
Loss of chromosome 7 or del(7q)monosomy 7, 7q deletion, or loss of 7q-7/del(7q)
Loss of chromosome 13 or del(13q)11q deletion+8
del(11q)12p deletion or loss of 12pdel(12p)/t(12p)/add(11p)
del(12p) or t(12p)Monosomy 13 or 13q deletioni(17q), -17/add(17p) or del(17p)
isochromosome 17q or t(17p)17p deletion or loss of 17p, isochromosome 17qdel(20q)
idic(X)(q13)idic(X)(q13)idci(X)(q13)
Balanced abnormalitiesDefining somatic mutationsGene mutations
t(11;16)(q23.3;p13.3)ASXL1ASXL1
t(3;21)(q26.2;q22.1)BCORBCOR
t(1;3)(p36.3;q21.2)EZH2EZH2
t(2;11)(p21;p23.3)SF3B1RUNX1
t(5;12)(q32;p13.2)SRSF2SF3B1
t(5;7)(q32;q11.2)STAG2SRSF2
t(5;17)(q32;p13.2)U2AF1STAG2
t(5;10)(q32;q21)ZRSR2U2AF1
t(3;5)(q25.3;q35.1)ZRSR2

Table 3 . Comparison of 2017 and 2022 European LeukmiaNet-acute myeloid leukemia risk classification.

Risk category2017 ELN2022 ELN
Favorablet(8;21)(q22;q22.1);RUNX1-RUNX1T1t(8;21)(q22;q22.1)/RUNX1::RUNX1T1
inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11
Mutated NPM1 without FLT3-ITD or with FLT3-ITDlow*Mutated NPM1 without FLT3-ITD
Biallelic mutated CEBPAbZIP in-frame mutated CEBPA
IntermediateMutated NPM1 with FLT3-ITDhighMutated NPM1 with FLT3-ITD
Wild-type NPM1 without FLT3-ITD or with FLT3-ITDlow (without adverse-risk genetic lesions)Wild-type NPM1 with FLT3-ITD (without adverse-risk genetic lesions)
t(9;11)(p21.3;q23.3)/MLLT3::KMT2At(9;11)(p21.3;q23.3)/MLLT3::KMT2A
Cytogenetic abnormalities not classified as favorable or adverseCytogenetic and/or molecular abnormalities not classified as favorable or adverse
Adverset(6;9)(p23.3;q34.10);DEK-NUP214t(6;9)(p23.3;q34.10)/DEK::NUP214
t(v;11q23.3);KMT2A-rearrangedt(v;11q23.3)/KMT2A-rearranged
t(9;22)(q34.1;q11.2);BCR-ABL1t(9;22)(q34.1;q11.2)/BCR::ABL1
t(8;16)(p11.2;p13.3)/KAT6A::CREBBP
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM(EVI1)inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1)
t(3q26.2;v)/MECOME(EVI1)-rearranged
-5 or del(5q); -7; -17/abn(17p)-5 or del(5q); -7; -17/abn(17p)
Complex karyotype, monosomal karyotypeComplex karyotype, monosomal karyotype
Mutated RUNX1, ASXL1Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
Mutated TP53Mutated TP53

* FLT3: low Low allelic ratio (< 0.5), high High allelic ratio(≥ 0.5).


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