Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia

被引：6

作者：

Eckardt, Jan-Niklas ^{[1
]}

Stasik, Sebastian ^{[1
]}

Roellig, Christoph ^{[1
]}

Petzold, Andreas ^{[2
]}

Sauer, Tim ^{[3
,4
]}

Scholl, Sebastian ^{[5
]}

Hochhaus, Andreas ^{[5
]}

Crysandt, Martina ^{[6
]}

Bruemmendorf, Tim H. ^{[6
]}

Naumann, Ralph ^{[7
]}

Steffen, Bjoern ^{[8
]}

Kunzmann, Volker ^{[9
]}

Einsele, Hermann ^{[9
]}

Schaich, Markus ^{[10
]}

Burchert, Andreas ^{[11
]}

Neubauer, Andreas ^{[11
]}

Schaefer-Eckart, Kerstin ^{[12
,13
]}

Schliemann, Christoph ^{[14
]}

Krause, Stefan W. ^{[15
]}

Herbst, Regina ^{[16
]}

Haenel, Mathias ^{[16
]}

Hanoun, Maher ^{[17
]}

Kaiser, Ulrich ^{[18
]}

Kaufmann, Martin ^{[19
]}

Racil, Zdenek ^{[20
]}

Mayer, Jiri ^{[20
]}

Oelschlaegel, Uta ^{[1
]}

Berdel, Wolfgang E. ^{[14
]}

Ehninger, Gerhard ^{[1
]}

Serve, Hubert ^{[8
]}

Mueller-Tidow, Carsten ^{[3
,4
]}

Platzbecker, Uwe ^{[21
]}

Baldus, Claudia D. ^{[22
]}

Dahl, Andreas ^{[2
]}

Schetelig, Johannes ^{[1
,23
]}

Bornhaeuser, Martin ^{[1
,24
,25
]}

Middeke, Jan Moritz ^{[1
]}

Thiede, Christian ^{[1
]}

机构：

[1] Univ Hosp Carl Gustav Carus, Dept Internal Med 1, Dresden, Germany

[2] Tech Univ Dresden, Dresden Concept Genome Ctr, Ctr Mol & Cellular Bioengn, Dresden, Germany

[3] Univ Hosp Heidelberg, German Canc Res Ctr DKFZ, Heidelberg, Germany

[4] Univ Hosp Heidelberg, Med Clin 5, Heidelberg, Germany

[5] Jena Univ Hosp, Klin Innere Med 2, Jena, Germany

[6] Univ Hosp RWTH Aachen, Dept Hematol Oncol Hemostaseol & Cell Therapy, Aachen, Germany

[7] St Marien Hosp Siegen, Med Clin 3, Siegen, Germany

[8] Univ Hosp Frankfurt, Med Clin 2, Frankfurt, Germany

[9] Univ Hosp Wurzburg, Med Clin & Policlin 2, Wurzburg, Germany

[10] Rems Murr Hosp, Dept Hematol Oncol & Palliat Care, Winnenden, Germany

[11] Philipps Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany

[12] Paracelsus Med Privatuniv, Dept Internal Med 5, Nurnberg, Germany

[13] Univ Hosp Nuremberg, Nurnberg, Germany

[14] Univ Hosp Munster, Dept Med A, Munster, Germany

[15] Univ Hosp Erlangen, Med Clin 5, Erlangen, Germany

[16] Chemnitz Hosp AG, Med Clin 3, Chemnitz, Germany

[17] Univ Hosp Essen, Dept Hematol, Essen, Germany

[18] St Bernward Hosp, Med Clin 2, Hildesheim, Germany

[19] Robert Bosch Krankenhaus, Dept Hematol Oncol & Palliat Care, Stuttgart, Germany

[20] Masaryk Univ Hosp, Dept Internal Med Hematol & Oncol, Brno, Czech Republic

[21] Univ Hosp Leipzig, Med Clin Hematol & Celltherapy 1, Leipzig, Germany

[22] Univ Hosp Kiel, Dept Internal Med, Kiel, Germany

[23] DKMS Clin Trials Unit, Dresden, Germany

[24] German Consortium Translat Canc Res DKFZ, Heidelberg, Germany

[25] Natl Ctr Tumor Dis NCT, Dresden, Germany

来源：

LEUKEMIA | 2023年 / 37卷 / 12期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; IKAROS GENE; PROGNOSTIC-SIGNIFICANCE; TRANSCRIPTION FACTOR; BINDING PROTEINS; ADULT PATIENTS; DELETION; IDENTIFICATION; DIFFERENTIATION; LENALIDOMIDE;

D O I：

10.1038/s41375-023-02061-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. In a multicenter cohort of 1606 newly diagnosed and intensively treated adult AML patients, we found IKZF1 alterations in 45 cases with a mutational hotspot at N159S. AML with mutated IKZF1 was associated with alterations in RUNX1, GATA2, KRAS, KIT, SF3B1, and ETV6, while alterations of NPM1, TET2, FLT3-ITD, and normal karyotypes were less frequent. The clinical phenotype of IKZF1-mutated AML was dominated by anemia and thrombocytopenia. In both univariable and multivariable analyses adjusting for age, de novo and secondary AML, and ELN2022 risk categories, we found mutated IKZF1 to be an independent marker of adverse risk regarding complete remission rate, event-free, relapse-free, and overall survival. The deleterious effects of mutated IKZF1 also prevailed in patients who underwent allogeneic hematopoietic stem cell transplantation (n = 519) in both univariable and multivariable models. These dismal outcomes are only partially explained by the hotspot mutation N159S. Our findings suggest a role for IKZF1 mutation status in AML risk modeling.

引用

页码：2395 / 2403

页数：9

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