Influence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletion

被引：7

作者：

Montoro, Maria Julia ^{[1
]}

Palomo, Laura ^{[1
]}

Haferlach, Claudia ^{[2
]}

Acha, Pamela ^{[3
]}

Chan, Onyee ^{[4
]}

Navarro, Victor ^{[5
]}

Kubota, Yasuo ^{[6
]}

Schulz, Felicitas Isabel ^{[7
]}

Meggendorfer, Manja ^{[2
]}

Briski, Robert ^{[8
]}

Al Ali, Najla ^{[4
]}

Xicoy, Blanca ^{[3
]}

Lopez-Cadenas, Felix ^{[9
]}

Bosch, Francesc ^{[1
]}

Gonzalez, Teresa ^{[10
]}

Eder, Lea Naomi ^{[11
]}

Jerez, Andres ^{[12
]}

Wang, Yu-Hung ^{[13
]}

Campagna, Alessia ^{[14
,15
]}

Santini, Valeria ^{[16
]}

del Castillo, Teresa Bernal ^{[17
]}

Such, Esperanza ^{[18
]}

Tien, Hwei-Fang ^{[19
]}

Varela, Nicolas Diaz ^{[17
]}

Platzbecker, Uwe ^{[20
]}

Haase, Detlef ^{[11
]}

Diez-Campelo, Maria ^{[10
]}

Della Porta, Matteo ^{[14
,15
]}

Garcia-Manero, Guillermo ^{[8
]}

Wiseman, Daniel H. ^{[13
]}

Germing, Ulrich ^{[7
]}

Maciejewski, Jaroslaw P. ^{[6
]}

Komrokji, Rami S. ^{[4
]}

Sole, Francesc ^{[3
]}

Haferlach, Torsten ^{[2
]}

Valcarcel, David ^{[1
]}

机构：

[1] Vall dHebron Barcelona Hosp Campus, Vall dHebron Inst Oncol, Dept Hematol, Paseo Vall Hebron 119-129, Barcelona 08006, Spain

[2] MLL Munich Leukemia Lab, Munich, Germany

[3] Inst Recerca Leucemia Josep Carreras, MDS Grp, Barcelona, Spain

[4] H Lee Mofitt Canc Ctr, Dept Malignant Hematol, Tampa, FL USA

[5] Vall dHebron Inst Oncol, Oncol Data Sci Grp, Barcelona, Spain

[6] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH USA

[7] Heinrich Heine Univ, Dept Hematol Oncol & Clin Immunol, Univ Hosp Dusseldorf, Dusseldorf, Germany

[8] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA

[9] Hosp del Mar, Dept Hematol, Barcelona, Spain

[10] Hosp Univ Salamanca, Dept Hematol, Inst Invest Biomed Salamanca, Salamanca, Spain

[11] Georg August Univ Gottingen, Univ Med Ctr Gottingen, Clin Hematol & Med Oncol, Gottingen, Germany

[12] Hosp Morales Meseguer, Dept Ophthalmol, Murcia 30008, Spain

[13] Univ Manchester, Div Canc Sci, Epigenet Haematopoiesis Lab, Manchester, England

[14] Humanitas Clin & Res Ctr IRCCS, Dept Neurosurg, Milan, Italy

[15] Humanitas Univ, Milan, Italy

[16] Univ Florence, MDS Unit, Hematol, Azienda Osped Univ Careggi, Florence, Italy

[17] Hosp Univ Cent Asturias, Inst Invest Sanitaria Principado Asturias ISPA, Translat Microbiol, Inst Invest Principado Asturias, Oviedo, Spain

[18] Hosp La Fe, Serv Hematol, Valencia, Spain

[19] Natl Taiwan Univ Hosp, Dept Internal Med, Div Hematol, Taipei, Taiwan

[20] Univ Hosp Leipzig, Dept Hematol, Dresden, Germany

来源：

BLOOD | 2024年 / 144卷 / 16期

基金：

欧盟地平线“2020”;

关键词：

HEALTH-ORGANIZATION CLASSIFICATION; PROGNOSTIC IMPACT; DEL(5Q); MDS; CHROMOSOME-5;

D O I：

10.1182/blood.2024023840

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twentyfour percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic mutations. TP53-multihit alterations were predictive of an increased risk of leukemic transformation. The impact of monoallelic alterations was dependent on the variant allele frequency (VAF); patients with TP53monoallelic mutations and VAF <20% exhibited behavior similar to TP53 wild type, and those with TP53-monoallelic mutations and VAF >= 20% presented outcomes equivalent to TP53-multihit patients. This study underscores the importance of considering TP53 allelic state and VAF in the risk stratification and treatment decision-making process for patients with MDS-del(5q).

引用

页码：1722 / 1731

页数：10

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