Blood Res (2024) 59:15
Published online April 15, 2024
https://doi.org/10.1007/s44313-024-00016-8
© The Korean Society of Hematology
Correspondence to : *Hee Sue Park
hsmed22@chungbuk.ac.kr
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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
Blood Res 2024; 59():
Published online April 15, 2024 https://doi.org/10.1007/s44313-024-00016-8
Copyright © The Korean Society of Hematology.
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
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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.
WHO2016 | WHO2022 | ICC | |||
---|---|---|---|---|---|
Classification | Blast (%) | Classification | Blast (%) | Classification | Blast (%) |
AML with recurrent genetic abnormalities | AML with defining genetic abnormalities | AML 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 | ≥ 20 | AML 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 | ≥ 20 | AML 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 | ≥ 20 | AML 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 | ≥ 20 | AML with BCR::ABL1 fusion | ≥ 20 | AML with t(9;22)(22)(q34.1;q11.2)/BCR::ABL1 | ≥ 20 |
AML with t(1;22)(p13.3;q13.1);RBM15::MLK1 | ≥ 20 | AML with RBM15::MRTFA fusion | . | ≥ 10 | |
AML with mutated NPM1 | . | AML with NPM1 mutation | AML with mutated NPM1 | ≥ 10 | |
AML with biallelic mutation of CEBPA | . | AML with CEBPA mutation | ≥ 20 | AML with mutated bZIP CEBPA | ≥ 10 |
(provisional) AML with mutated RUNX1 | ≥ 20 | AML with NUP98 rearrangement | . | AML with TP53 | ≥ 20 |
AML myeloid leukemia, myelodysplasia-related | ≥ 20 | AML with other rare recurring translocations | ≥ 10 | ||
AML with other defined genetic alteration | ≥ 20 | AML 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.
WHO2016 | WHO2022 | ICC |
---|---|---|
Complex karyotype (≥ 3 abnormalities) | Cytogenetic abnormalities | Cytogenetic abnormalities |
Unbalanced abnormalities | Complex karyotype (≥ 3 abnormalities) | Complex karyotype (≥ 3 abnormalities) |
del(5q) or t(5q) | 5q deletion or loss of 5q | del(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 12p | del(12p)/t(12p)/add(11p) |
del(12p) or t(12p) | Monosomy 13 or 13q deletion | i(17q), -17/add(17p) or del(17p) |
isochromosome 17q or t(17p) | 17p deletion or loss of 17p, isochromosome 17q | del(20q) |
idic(X)(q13) | idic(X)(q13) | idci(X)(q13) |
Balanced abnormalities | Defining somatic mutations | Gene mutations |
t(11;16)(q23.3;p13.3) | ASXL1 | ASXL1 |
t(3;21)(q26.2;q22.1) | BCOR | BCOR |
t(1;3)(p36.3;q21.2) | EZH2 | EZH2 |
t(2;11)(p21;p23.3) | SF3B1 | RUNX1 |
t(5;12)(q32;p13.2) | SRSF2 | SF3B1 |
t(5;7)(q32;q11.2) | STAG2 | SRSF2 |
t(5;17)(q32;p13.2) | U2AF1 | STAG2 |
t(5;10)(q32;q21) | ZRSR2 | U2AF1 |
t(3;5)(q25.3;q35.1) | ZRSR2 |
Table 3 . Comparison of 2017 and 2022 European LeukmiaNet-acute myeloid leukemia risk classification.
Risk category | 2017 ELN | 2022 ELN |
---|---|---|
Favorable | t(8;21)(q22;q22.1);RUNX1-RUNX1T1 | t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 |
inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11 | inv(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 CEBPA | bZIP in-frame mutated CEBPA | |
Intermediate | Mutated NPM1 with FLT3-ITDhigh | Mutated 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::KMT2A | t(9;11)(p21.3;q23.3)/MLLT3::KMT2A | |
Cytogenetic abnormalities not classified as favorable or adverse | Cytogenetic and/or molecular abnormalities not classified as favorable or adverse | |
Adverse | t(6;9)(p23.3;q34.10);DEK-NUP214 | t(6;9)(p23.3;q34.10)/DEK::NUP214 |
t(v;11q23.3);KMT2A-rearranged | t(v;11q23.3)/KMT2A-rearranged | |
t(9;22)(q34.1;q11.2);BCR-ABL1 | t(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 karyotype | Complex karyotype, monosomal karyotype | |
Mutated RUNX1, ASXL1 | Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 | |
Mutated TP53 | Mutated TP53 |
* FLT3: low Low allelic ratio (< 0.5), high High allelic ratio(≥ 0.5).
Hyunwoo Kim, Ja Young Lee, Sinae Yu, Eunkyoung Yoo, Hye Ran Kim, Sang Min Lee and Won Sik Lee
Blood Res 2024; 59():Sahar Jalilivand, Maryam Nabigol, Mehdi Bakhtiyaridovvombaygi and Ahmad Gharehbaghian
Blood Res 2024; 59():Raziyeh Hakak, Behzad Poopak and Ahmad Majd
Blood Res 2024; 59():