Clinical Outcomes of Acute Myeloid Leukemia Patients Harboring the RUNX1 Mutation: Is It Still an Unfavorable Prognosis? A Cohort Study and Meta-Analysis

被引：5

作者：

Rungjirajittranon, Tarinee ^{[1
]}

Siriwannangkul, Theerapat ^{[1
]}

Kungwankiattichai, Smith ^{[1
]}

Leelakanok, Nattawut ^{[2
]}

Rotchanapanya, Wannaphorn ^{[3
]}

Vittayawacharin, Pongthep ^{[1
]}

Mekrakseree, Benjamaporn ^{[4
]}

Kulchutisin, Kamolchanok ^{[5
]}

Owattanapanich, Weerapat ^{[1
]}

机构：

[1] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Med,Div Hematol, Bangkok 10700, Thailand

[2] Burapha Univ, Fac Pharmaceut Sci, Dept Clin Pharm, Chon Buri 20131, Thailand

[3] Chiangrai Prachanukroh Hosp, Dept Med, Chiangrai 57000, Thailand

[4] Rajavithi Hosp, Dept Med, Div Hematol, Bangkok 10400, Thailand

[5] Mahidol Univ, Siriraj Hosp, Fac Med, Bangkok 10700, Thailand

来源：

CANCERS | 2022年 / 14卷 / 21期

关键词：

acute myeloid leukemia; genetic; molecular; mutation; next-generation sequencing; RUNX1; HEALTH-ORGANIZATION CLASSIFICATION; GENE-MUTATIONS; AML; DIAGNOSIS; RECOMMENDATIONS; FREQUENCY;

D O I：

10.3390/cancers14215239

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1(mut)) has an adverse prognosis based on the 2022 European LeukemiaNet risk stratification. However, the WHO classifications of 2022 removed RUNX1 mutations from the unique entity because of various prognoses and treatment outcomes. Intriguingly, the overall survival (OS) and relapse-free survival (RFS) outcomes were similar in patients who had de novo AML with intermediate-risk cytogenetics with and without RUNX1(mut). Our study endorsed an unfavorable prognosis of this entity. Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1(mut)) is considered to have an unfavorable prognosis. However, recent studies have reported comparable survival outcomes with wild-type RUNX1 (RUNX1(wt)). To assess the clinical outcomes of AML with and without RUNX1(mut), we performed a prospective cohort study and systematic review and meta-analysis. The study enrolled 135 patients (27 with RUNX1(mut); 108 with RUNX1(w)(t)). There were no significant differences in the median OS and RFS of the RUNX1(mut) and RUNX1(wt) groups (9.1 vs. 12.2 months; p = 0.268 and 7.8 vs. 14.6 months; p = 0.481, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics showed similar outcomes. Our meta-analysis pooled data from 23 studies and our study. The complete remission rate was significantly lower in the RUNX1(mut) group (pooled odds ratio: 0.42). The OS, RFS, and event-free survival rates also favored the RUNX1(wt) group (pooled risk ratios: 1.36, 1.37, and 1.37, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics demonstrated nearly identical OS and RFS outcomes. This study confirms that patients with AML and RUNX1(mut) had poor prognoses. Nonetheless, in de novo AML with intermediate-risk cytogenetics, the survival outcomes of both groups were comparable.

引用

页数：20

共 57 条

[1] 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

[2] Next-generation sequencing reveals gene mutations landscape and clonal evolution in patients with acute myeloid leukemia [J].

Chen, Xiao ;

Zhu, Han ;

Qiao, Chun ;

Zhao, Sishu ;

Liu, Lu ;

Wang, Yan ;

Jin, Huimin ;

Qian, Sixuan ;

Wu, Yujie .

HEMATOLOGY, 2021, 26 (01) :111-122

[3] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia [J].

Cheson, BD ;

Bennett, JM ;

Kopecky, KJ ;

Büchner, T ;

Willman, CL ;

Estey, EH ;

Schiffer, CA ;

Döhner, H ;

Tallman, MS ;

Lister, TA ;

LoCocco, F ;

Willemze, R ;

Biondi, A ;

Hiddemann, W ;

Larson, RA ;

Löwenberg, B ;

Sanz, MA ;

Head, DR ;

Ohno, R ;

Bloomfield, CD .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) :4642-4649

[4] The leukemia strikes back: a review of pathogenesis and treatment of secondary AML [J].

Cheung, Edna ;

Perissinotti, Anthony J. ;

Bixby, Dale L. ;

Burke, Patrick W. ;

Pettit, Kristen M. ;

Benitez, Lydia L. ;

Brown, Julia ;

Scappaticci, Gianni B. ;

Marini, Bernard L. .

ANNALS OF HEMATOLOGY, 2019, 98 (03) :541-559

[5] Mutations in AML: prognostic and therapeutic implications [J].

DiNardo, Courtney D. ;

Cortes, Jorge E. .

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM, 2016, :348-355

[6] Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN [J].

Doehner, Hartmut ;

Wei, Andrew H. ;

Appelbaum, Frederick R. ;

Craddock, Charles ;

DiNardo, Courtney D. ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Godley, Lucy A. ;

Hasserjian, Robert P. ;

Larson, Richard A. ;

Levine, Ross L. ;

Miyazaki, Yasushi ;

Niederwieser, Dietger ;

Ossenkoppele, Gert ;

Roellig, Christoph ;

Sierra, Jorge ;

Stein, Eytan M. ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wang, Jianxiang ;

Wierzbowska, Agnieszka ;

Lowenberg, Bob .

BLOOD, 2022, 140 (12) :1345-1377

[7] Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].

Doehner, Hartmut ;

Estey, Elihu ;

Grimwade, David ;

Amadori, Sergio ;

Appelbaum, Frederick R. ;

Buechner, Thomas ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Larson, Richard A. ;

Levine, Ross L. ;

Lo-Coco, Francesco ;

Naoe, Tomoki ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. ;

Sanz, Miguel ;

Sierra, Jorge ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wei, Andrew H. ;

Lowenberg, Bob ;

Bloomfield, Clara D. .

BLOOD, 2017, 129 (04) :424-447

[8]

Gaidzik VI, 2016, LEUKEMIA, V30, P2160, DOI 10.1038/leu.2016.126

[9] RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes [J].

Greif, Philipp A. ;

Konstandin, Nikola P. ;

Metzeler, Klaus H. ;

Herold, Tobias ;

Pasalic, Zlatana ;

Ksienzyk, Bianka ;

Dufour, Annika ;

Schneider, Friederike ;

Schneider, Stephanie ;

Kakadia, Purvi M. ;

Braess, Jan ;

Sauerland, Maria Cristina ;

Berdel, Wolfgang E. ;

Buechner, Thomas ;

Woermann, Bernhard J. ;

Hiddemann, Wolfgang ;

Spiekermann, Karsten ;

Bohlander, Stefan K. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (12) :1909-1915

[10] Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome [J].

Grob, Tim ;

Al Hinai, Adil S. A. ;

Sanders, Mathijs A. ;

Kavelaars, Francois G. ;

Rijken, Melissa ;

Gradowska, Patrycja L. ;

Biemond, Bart J. ;

Breems, Dimitri A. ;

Maertens, Johan ;

Kooy, Marinus van Marwijk ;

Pabst, Thomas ;

de Weerdt, Okke ;

Ossenkoppele, Gert J. ;

van de Loosdrecht, Arjan A. ;

Huls, Gerwin A. ;

Cornelissen, Jan J. ;

Beverloo, H. Berna ;

Lowenberg, Bob ;

Jongen-Lavrencic, Mojca ;

Valk, Peter J. M. .

BLOOD, 2022, 139 (15) :2347-2354

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