The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome

被引：3

作者：

Kuelp, Marius ^{[1
,2
]}

Larghero, Patrizia ^{[1
]}

Alten, Julia ^{[3
]}

Cario, Gunnar ^{[3
]}

Eckert, Cornelia ^{[4
]}

Caye-Eude, Aurelie ^{[5
,6
]}

Cave, Helene ^{[5
,6
]}

Schmachtel, Tessa ^{[2
]}

Bardini, Michela ^{[7
]}

Cazzaniga, Giovanni ^{[7
,8
]}

De Lorenzo, Paola ^{[9
]}

Valsecchi, Maria Grazia ^{[10
]}

Bonig, Halvard ^{[11
,12
,13
]}

Meyer, Claus ^{[1
]}

Rieger, Michael A. ^{[2
,14
,15
]}

Marschalek, Rolf ^{[1
]}

机构：

[1] Goethe Univ, Inst Pharmaceut Biol, Diagnost Ctr Acute Leukemia DCAL, Frankfurt Am Main, Germany

[2] Goethe Univ Hosp Frankfurt, Dept Med Hematol Oncol, Frankfurt Am Main, Germany

[3] Univ Med Ctr Schleswig Holstein, Dept Pediat, Campus Kiel, Lubeck, Germany

[4] Charite Univ Med Berlin, Dept Pediat Hematol & Oncol, Berlin, Germany

[5] Hop Robert Debre, AP HP, Genet Dept, F-75019 Paris, France

[6] Univ Paris Cite, Inst Rech St Louis, Inserm U1131, F-75010 Paris, France

[7] Univ Milano Bicocca, San Gerardo Hosp, Fdn Monza & Brianza Bambino MBBM, Ctr Ric Tettamanti,Pediat, Monza, Italy

[8] Univ Milano Bicocca, Sch Med & Surg, Genet, Monza, Italy

[9] Univ Milano Bicocca, Pediat Clin, Stat Sect, Monza, Italy

[10] Univ Milano Bicocca, Ctr Bioinformat Biostat & Bioimaging, Monza, Italy

[11] Goethe Univ, Inst Transfus Med & Immunohematol, Frankfurt Am Main, Germany

[12] German Red Cross Blood Serv Baden Wurttemberg Hess, Frankfurt Am Main, Germany

[13] Univ Washington, Dept Med, Div Hematol, Sch Med, Seattle, WA USA

[14] German Canc Consortium, DKTK & German Canc Res Ctr DKZF, Heidelberg, Germany

[15] Cardio Pulm Inst, Frankfurt Am Main, Germany

来源：

LEUKEMIA | 2023年 / 37卷 / 06期

关键词：

TRANSCRIPTION FACTOR; CELL IDENTITY; RESPONSE GENES; A EGR-1; PAX5; PROLIFERATION; INFLAMMATION; COREPRESSOR; INTEGRATION; DISRUPTION;

D O I：

10.1038/s41375-023-01895-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

KMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.

引用

页码：1216 / 1233

页数：18

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