Comparison of acute myeloid leukemia and myelodysplastic syndromes with TP53 aberrations

被引：10

作者：

Dutta, Sayantanee ^{[1
]}

Moritz, Jennifer ^{[1
]}

Pregartner, Gudrun ^{[2
]}

Thallinger, Gerhard G. ^{[3
,4
]}

Brandstaetter, Ilona ^{[1
]}

Lind, Karin ^{[1
]}

Rezania, Simin ^{[1
]}

Lyssy, Freya ^{[4
]}

Reinisch, Andreas ^{[1
,5
]}

Zebisch, Armin ^{[1
,6
]}

Berghold, Andrea ^{[2
]}

Woelfler, Albert ^{[1
]}

Sill, Heinz ^{[1
,4
]}

机构：

[1] Med Univ Graz, Div Hematol, Auenbruggerpl 38, A-8036 Graz, Austria

[2] Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria

[3] Graz Univ Technol, Inst Biomed Informat, Graz, Austria

[4] BioTechMed Graz, Graz, Austria

[5] Med Univ Graz, Dept Blood Grp Serol & Transfus Med, Graz, Austria

[6] Med Univ Graz, Otto Loewi Res Ctr Vasc Biol Immunol & Inflammat, Div Pharmacol, Graz, Austria

来源：

ANNALS OF HEMATOLOGY | 2022年 / 101卷 / 04期

基金：

奥地利科学基金会;

关键词：

TP53; Acute myeloid leukemia; Myelodysplastic syndromes; Stem cell disorder; EAp53 and RFS score; STEM-CELLS; P53; MUTATIONS; CLASSIFICATION;

D O I：

10.1007/s00277-022-04766-2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

TP53 aberrations are found in approximately 10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and are considered early driver events affecting leukemia stem cells. In this study, we compared features of a total of 84 patients with these disorders seen at a tertiary cancer center. Clinical and cytogenetic characteristics as well as immunophenotypes of immature blast cells were similar between AML and MDS patients. Median overall survival (OS) was 226 days (95% confidence interval [CI], 131-300) for the entire cohort with an estimated 3-year OS rate of 11% (95% CI, 6-22). OS showed a significant difference between MDS (median, 345 days; 95% CI, 235-590) and AML patients (median, 91 days; 95% CI, 64-226) which is likely due to a different co-mutational pattern as revealed by next-generation sequencing. Transformation of TP53 aberrant MDS occurred in 60.5% of cases and substantially reduced their survival probability. Cox regression analysis revealed treatment class and TP53 variant allele frequency as prognostically relevant parameters but not the TP53-specific prognostic scores EAp53 and RFS. These data emphasize similarities between TP53 aberrant AML and MDS and support previous notions that they should be classified and treated as a distinct disorder.

引用

页码：837 / 846

页数：10

共 45 条

[1] Prediction of acute myeloid leukaemia risk in healthy individuals [J].

Abelson, Sagi ;

Collord, Grace ;

Ng, Stanley W. K. ;

Weissbrod, Omer ;

Cohen, Netta Mendelson ;

Niemeyer, Elisabeth ;

Barda, Noam ;

Zuzarte, Philip C. ;

Heisler, Lawrence ;

Sundaravadanam, Yogi ;

Luben, Robert ;

Hayat, Shabina ;

Wang, Ting Ting ;

Zhao, Zhen ;

Cirlan, Julia ;

Pugh, Trevor J. ;

Soave, David ;

Ng, Karen ;

Latimer, Calli ;

Hardy, Claire ;

Raine, Keiran ;

Jones, David ;

Hoult, Diana ;

Britten, Abigail ;

McPherson, John D. ;

Johansson, Mattias ;

Mbabaali, Faridah ;

Eagles, Jenna ;

Millers, Jessica K. ;

Pasternack, Danielle ;

Timms, Lee ;

Krzyzanowski, Paul ;

Awadalla, Philip ;

Costa, Rui ;

Segal, Eran ;

Bratman, Scott, V ;

Beer, Philip ;

Behjati, Sam ;

Martincorena, Inigo ;

Wang, Jean C. Y. ;

Bowles, Kristian M. ;

Ramon Quiros, J. ;

Karakatsani, Anna ;

La Vecchia, Carlo ;

Trichopoulou, Antonia ;

Salamanca-Fernandez, Elena ;

Huerta, Jose M. ;

Barricarte, Aurelio ;

Travis, Ruth C. ;

Tumino, Rosario .

NATURE, 2018, 559 (7714) :400-+

[2] The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [J].

Arber, Daniel A. ;

Orazi, Attilio ;

Hasserjian, Robert ;

Thiele, Jurgen ;

Borowitz, Michael J. ;

Le Beau, Michelle M. ;

Bloomfield, Clara D. ;

Cazzola, Mario ;

Vardiman, James W. .

BLOOD, 2016, 127 (20) :2391-2405

[3] Clinical Effect of Point Mutations in Myelodysplastic Syndromes [J].

Bejar, Rafael ;

Stevenson, Kristen ;

Abdel-Wahab, Omar ;

Galili, Naomi ;

Nilsson, Bjoern ;

Garcia-Manero, Guillermo ;

Kantarjian, Hagop ;

Raza, Azra ;

Levine, Ross L. ;

Neuberg, Donna ;

Ebert, Benjamin L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (26) :2496-2506

[4] Implications ofTP53allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes [J].

Bernard, Elsa ;

Nannya, Yasuhito ;

Hasserjian, Robert P. ;

Devlin, Sean M. ;

Tuechler, Heinz ;

Medina-Martinez, Juan S. ;

Yoshizato, Tetsuichi ;

Shiozawa, Yusuke ;

Saiki, Ryunosuke ;

Malcovati, Luca ;

Levine, Max F. ;

Arango, Juan E. ;

Zhou, Yangyu ;

Sole, Francesc ;

Cargo, Catherine A. ;

Haase, Detlef ;

Creignou, Maria ;

Germing, Ulrich ;

Zhang, Yanming ;

Gundem, Gunes ;

Sarian, Araxe ;

van de Loosdrecht, Arjan A. ;

Jadersten, Martin ;

Tobiasson, Magnus ;

Kosmider, Olivier ;

Follo, Matilde Y. ;

Thol, Felicitas ;

Pinheiro, Ronald F. ;

Santini, Valeria ;

Kotsianidis, Ioannis ;

Boultwood, Jacqueline ;

Santos, Fabio P. S. ;

Schanz, Julie ;

Kasahara, Senji ;

Ishikawa, Takayuki ;

Tsurumi, Hisashi ;

Takaori-Kondo, Akifumi ;

Kiguchi, Toru ;

Polprasert, Chantana ;

Bennett, John M. ;

Klimek, Virginia M. ;

Savona, Michael R. ;

Belickova, Monika ;

Ganster, Christina ;

Palomo, Laura ;

Sanz, Guillermo ;

Ades, Lionel ;

Della Porta, Matteo Giovanni ;

Smith, Alexandra G. ;

Werner, Yesenia .

NATURE MEDICINE, 2020, 26 (10) :1549-+

[5] Loss of RAF kinase inhibitor protein is involved in myelomonocytic differentiation an aggravates RAS-driven myeloid leukemogenesis [J].

Caraffini, Veronica ;

Geiger, Olivia ;

Rosenberger, Angelika ;

Hatzl, Stefan ;

Perfler, Bianca ;

Berg, Johannes L. ;

Lim, Clarice ;

Strobl, Herbert ;

Kashofer, Karl ;

Schauer, Silvia ;

Beham-Schmid, Christine ;

Hoefler, Gerald ;

Geissler, Klaus ;

Quehenberger, Franz ;

Kolch, Walter ;

Athineos, Dimitris ;

Blyth, Karen ;

Woelfler, Albert ;

Sill, Heinz ;

Zebisch, Armin .

HAEMATOLOGICA, 2020, 105 (02) :375-386

[6] Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies [J].

Chao, Mark P. ;

Takimoto, Chris H. ;

Feng, Dong Dong ;

McKenna, Kelly ;

Gip, Phung ;

Liu, Jie ;

Volkmer, Jens-Peter ;

Weissman, Irving L. ;

Majeti, Ravindra .

FRONTIERS IN ONCOLOGY, 2020, 9

[7] Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level [J].

Chen, Jiahao ;

Kao, Yun-Ruei ;

Sun, Daqian ;

Todorova, Tihomira I. ;

Reynolds, David ;

Narayanagari, Swathi-Rao ;

Montagna, Cristina ;

Will, Britta ;

Verma, Amit ;

Steidl, Ulrich .

NATURE MEDICINE, 2019, 25 (01) :103-+

[8] Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations [J].

Ciurea, Stefan O. ;

Chilkulwar, Abhishek ;

Saliba, Rima M. ;

Chen, Julianne ;

Rondon, Gabriela ;

Patel, Keyur P. ;

Khogeer, Haitham ;

Shah, Abdul R. ;

Randolph, Brion V. ;

Perez, Jorge M. Ramos ;

Popat, Uday ;

Hosing, Chitra M. ;

Bashir, Qaiser ;

Mehta, Rohtesh ;

Al-Atrash, Gheath ;

Im, Jin ;

Khouri, Issa F. ;

Kebriaei, Partow ;

Champlin, Richard E. .

BLOOD, 2018, 131 (26) :2989-2992

[9] Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myelodysplasies (GFM) [J].

Cluzeau, Thomas ;

Sebert, Marie ;

Rahme, Ramy ;

Cuzzubbo, Stefania ;

Lehmann-Che, Jacqueline ;

Madelaine, Isabelle ;

Peterlin, Pierre ;

Beve, Blandine ;

Attalah, Habiba ;

Chermat, Fatiha ;

Miekoutima, Elsa ;

Rauzy, Odile Beyne ;

Recher, Christian ;

Stamatoullas, Aspasia ;

Willems, Lise ;

Raffoux, Emmanuel ;

Berthon, Celine ;

Quesnel, Bruno ;

Loschi, Michael ;

Carpentier, Antoine F. ;

Sallman, David A. ;

Komrokji, Rami ;

Walter-Petrich, Anouk ;

Chevret, Sylvie ;

Ades, Lionel ;

Fenaux, Pierre .

JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (14) :1575-+

[10] Sensitive and broadly applicable residual disease detection in acute myeloid leukemia using flow cytometry-based leukemic cell enrichment followed by mutational profiling [J].

Daga, Shruti ;

Rosenberger, Angelika ;

Kashofer, Karl ;

Heitzer, Ellen ;

Quehenberger, Franz ;

Halbwedl, Iris ;

Graf, Ricarda ;

Krisper, Nina ;

Prietl, Barbara ;

Hoefler, Gerald ;

Reinisch, Andreas ;

Zebisch, Armin ;

Sill, Heinz ;

Woelfler, Albert .

AMERICAN JOURNAL OF HEMATOLOGY, 2020, 95 (10) :1148-1157

← 1 2 3 4 5 →