Validation of the 5th edition of the World Health Organization and International Consensus Classification guidelines for TP53-mutated myeloid neoplasm in an independent international cohort
Year: 2025
Type: article
Study design: Observational Study
Abstract: The World Health Organization (WHO-5) and International Consensus Classification (ICC) acknowledge the poor prognosis of TP53 -mutated ( TP53 mut ) myeloid neoplasm (MN). However, there are substantial differences between the two classifications that may lead to under- or overestimation of the prognostic risk. We retrospectively applied WHO-5 and ICC to 603 MN cases harboring TP53 mut (variant allele frequency, VAF ≥ 2%). WHO-5 and ICC would not classify 64% and 20% of these cases as TP53 mut MN, respectively. Moreover, of those classified, 67.5% would be classified discrepantly. Primary drivers of discrepancies included: (i) prognostic importance of TP53 mut acute myeloid leukemia (AML), (ii) interaction of the blast percentage and allelic status, (iii) 17p.13.1 deletion detected by cytogenetics, (iv) complex karyotype (CK) as multi-hit equivalent, and (v) TP53 mut VAF threshold, we analyzed survival outcomes of each of these groups with an aim to provide clarity. TP53 mut AML was associated with significantly poor survival compared to TP53 -wild type TP53 wt AML, myelodysplasia-related (AML, MR 4.7 vs . 18.3 months; P < 0.0001), supporting its inclusion within TP53 mut MN as a distinct subentity. Secondly, the survival of TP53 mut with blast 10–19% was poor regardless of the allelic status. Thirdly, for cases with a single TP53 mut with VAF < 50%, 17p13.1 del or CK serve as practical surrogates of biallelic inactivation, obviating the need for an additional copy number analysis. Finally, TP53 mut AML, MDS multi-hit/multi-hit equivalent with VAF < 10% had significantly poorer survival compared to TP53 mut MDS VAF < 10% without CK and 17p del, and were comparable to those with VAF ≥ 10% (14.1 vs . 48.8 vs .7.8 months, P < 0.0001). Collectively, these findings address key areas of contention and provide valuable insights that will guide future revisions of the WHO and ICC classifications.
Source: Blood Cancer Journal
Authors: Mithun Vinod Shah, Kevin Hung, Anmol Baranwal, Gauri Wechalekar, Aref Al-Kali, Carla R. Toop, Patricia Greipp, Monika M. Kutyna, Aasiya Matin, Dariusz Ladon, Antoine Saliba, Dong Chen, Kebede Begna, Anna Brown, Danielle Rud, Mark R. Litzow, William J. Hogan, Peter Bardy, Talha Badar, Sharad Kumar, David T. Yeung, Mrinal M. Patnaik, James M. Foran, Rong He, Naseema Gangat, Mehrdad Hefazi, Hamish S. Scott, Cecilia Y. Arana Yi, Hassan Alkhateeb, Abhishek A. Mangaonkar, Daniel Thomas, Christopher N. Hahn, Attilio Orazi, Daniel A. Arber, Chung Hoow Kok, Ayalew Tefferi, Devendra Hiwase
Institutions: Mayo Clinic, Royal Adelaide Hospital, South Australian Health and Medical Research Institute, Central Adelaide Local Health Network, The University of Adelaide, South Australia Pathology, University of South Australia, Centre for Cancer Biology, Mayo Clinic in Florida, Mayo Clinic in Arizona, Texas Tech University Health Sciences Center, University of Chicago, SA Health
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
OpenAlex ID: W4410161291