Evidence-based risk stratification of myeloid neoplasms harboring <i>TP53</i> mutations

This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2025-03-14
DOI
https://doi.org/10.1182/bloodadvances.2024015238
Citations
13
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
23.01

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations

David T Yeung, Naseema Gangat, Aref Al‐Kali, Abhishek Avinash Mangaonkar et al.
13 citations
Blood Advances
Acute Myeloid Leukemia Research
23.01
article

Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations

David T Yeung, Naseema Gangat, Aref Al‐Kali, Abhishek Avinash Mangaonkar, Ayalew Tefferi, Sharad Kumar, Cecilia Arana Yi, Mithun Vinod Shah, Syed Naseem Shah, Monika Kutyna, James M. Foran, Attilio Orazi, Hamish S. Scott, Anmol Baranwal, Dariusz Ladon, Vedavyas Gannamani, Kevin Hung, Devendra Hiwase, Christopher N Hahn, Chung Hoow Kok, Hassan B. Alkhateeb, Anna Brown, Daniel A. Arber, Mrinal M. Patnaik, Patricia T. Greipp, Talha Badar, Rong Lucy He, Kebede H. Begna, William J. Hogan, Mark Robert Litzow, Danièl Thomas, Danielle Rud, Dong Chen, Peter Bardy, Shreyas Khanna, Carla Toop, Zoe Price
article en
13 citations

Abstract

This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.

Blood AdvancesVol. 9(13)
South Australia Pathology (AU), Texas Tech University (US), Royal Adelaide Hospital (AU), Mayo Clinic (US), The University of Texas at El Paso (US), University of South Australia (AU), Jacksonville College (US), WinnMed (US), University of Chicago (US), Women's and Children's Health Network (AU), Mayo Clinic in Arizona (US), Mayo Clinic Hospital (US), South Australian Health and Medical Research Institute (AU), Centre for Cancer Biology (AU), Mayo Clinic in Florida (US), Central Adelaide Local Health Network, The University of Adelaide (AU), Texas Tech University Health Sciences Center (US)
Cancer Australia, Medical Research Council, National Health and Medical Research Council
No poverty
Openalex Percentile: Top 0%
Acute Myeloid Leukemia Research
23.01
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.