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International Consensus Classification of acute lymphoblastic leukemia/lymphoma

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Abstract

The updated International Consensus Classification (ICC) of B-acute lymphoblastic leukemia (B-ALL) and T-acute lymphoblastic leukemia (T-ALL) includes both revisions to subtypes previously outlined in the 2016 WHO classification and several newly described entities. The ICC classification incorporates recent clinical, cytogenetic, and molecular data, with a particular emphasis on whole transcriptome analysis and gene expression (GEX) clustering studies. B-ALL classification is modified to further subclassify BCR::ABL1-positive B-ALL and hypodiploid B-ALL. Additionally, nine new categories of B-ALL are defined, including seven that contain distinguishing gene rearrangements, as well as two new categories that are characterized by a specific single gene mutation. Four provisional entities are also included in the updated B-ALL classification, although definitive identification of these subtypes requires GEX studies. T-ALL classification is also updated to incorporate BCL11B-activating rearrangements into early T-precursor (ETP) ALL taxonomy. Additionally, eight new provisional entities are added to the T-ALL subclassification. The clinical implications of the new entities are discussed, as are practical approaches to the use of different technologies in diagnosis. The enhanced specificity of the new classification will allow for improved risk stratification and optimized treatment plans for patients with ALL.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AYA:

Adolescents and young adults

B-ALL:

B-lymphoblastic leukemia

BCL11B-a:

BCL11B-activated

BCR::ABL1 + ALL-L:

BCR::ABL1 B-ALL with lymphoid only involvement

BCR::ABL1 + ALL-M:

BCR::ABL1-positive B-ALL with multilineage involvement

CDX2/UBTF:

B-ALL with UBTF::ATXN7L3/PAN3,CDX2

CML:

Chronic myeloid leukemia

ETP:

Early T precursor

FISH:

Fluorescence in situ hybridization

GEX:

Gene expression

ICC :

International Consensus Classification

IHC:

Immunohistochemistry

LBP:

Lymphoid blast phase

LMO1/2-r :

LMO1-rearranged or LMO2-rearranged

MPAL:

Mixed phenotype acute leukemia

NGS:

Next generation sequencing

NOS:

Not otherwise specified

PAX5alt:

PAX5-altered B-ALL

T-ALL:

T-lymphoblastic leukemia

TAL1/2-r:

TAL1-rearranged or TAL2-rearranged

TKIs:

Tyrosine kinase inhibitors

TS:

Transcriptome sequencing

WGS:

Whole genome sequencing (WGS)

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Acknowledgements

The authors thank the members of the working group including Elias Jabbour, Ching-Hon Pui, Kathryn Foucar, Nicola Goekbuget, Hartmut Doehner, and Mignon Loh, as well as Daniel Arber for thoughtful discussion. Additionally, the authors thank Dr. Qingsong Gao (St. Jude Children’s Research Hospital, Memphis, TN), who created Fig. 1.

Funding

A.S.D.: Financial support was received from P30 CA008748 (National Cancer Institute, National Institutes of Health).

C.G.M.: Financial support was received from P30 CA021765 and R35 CA197695 (National Cancer Institute, National Institutes of Health).

M.J.B.: Financial support was received from U10 CA180886 (National Cancer Institute, National Institutes of Health).

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  1. Amy S. Duffield

    Present address: Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA

Authors and Affiliations

  1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Amy S. Duffield

  2. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Charles G. Mullighan

  3. Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Michael J. Borowitz

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M.J.B. was the initial contact for this invited review, and all authors (A.S.D., C.G.M., and M.J.B.) performed the literature search and data analysis, and drafted and/or critically revised the work. All authors have made substantial contributions to this review, have read and approved the final version submitted, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Michael J. Borowitz.

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The contents of Tables 1, 2, 3, and 4 are similar to those published in “Arber DA et al. [78]” because the current review expands on the International Consensus Classification first described in the June 2022 manuscript; however, the contents of the current manuscript have not been copyrighted.

Conflict of interest

Authors A.S.D. and M.J.B. declare no competing interests. Author C.G.M. has received speaker (Illumina and Amgen) and consultant (Faze, Beam) honoraria, and receives research funding from AbbVie and Pfizer.

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Duffield, A.S., Mullighan, C.G. & Borowitz, M.J. International Consensus Classification of acute lymphoblastic leukemia/lymphoma. Virchows Arch 482, 11–26 (2023). https://doi.org/10.1007/s00428-022-03448-8

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  • DOI: https://doi.org/10.1007/s00428-022-03448-8

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