The prognostic factors in acute myeloid leukaemia with double‐mutated CCAAT/enhancer‐binding protein alpha <scp>(<i>CEBPA</i>dm</scp>)

Wei, Hui; Zhou, Chunlin; Liu, Bingcheng; Lin, Dong; Li, Yan; Wei, Shuning; Gong, Bin; Zhang, Guangji; Liu, Kaiqi; Gong, Xiaoyuan; Fang, Qiuyun; Liu, Yuntao; Qiu, Shaowei; Gu, Runxia; Song, Zhen; Chen, Jiayuan; Yang, Miao; Zhang, Junping; Jin, Jingjing; Wang, Ying; Mi, Yingchang; Wang, Jianxiang

doi:10.1111/bjh.18113

Cited by 5 publications

(5 citation statements)

References 19 publications

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“…Our previous studies have found that induction regimens including homoharringtonine and intermediate-dose cytarabine produced favorable outcomes in AML patients with CEBPA dm . [17][18][19] Given the relationship between immunophenotypes and the CEBPA mutation status, a scoring system was developed to identify AML with CEBPA-WHO based on immunophenotype and validated it internally and externally with good clinical performance. With this scoring system, we could preemptively identify AML patients with CEBPA WHO and choose an optimal induction regimen for them.…”

Section: Discussionmentioning

confidence: 99%

“…Induction therapies affect the clinical outcomes of AML with CEBPA mutation, either. Our previous studies found that the induction regimen including both homoharringtonine and intermediate‐dose cytarabine produced more favorable outcomes in AML patients with CEBPA dm with 3‐year RFS and OS at 84.7% and 92.8%, respectively, compared to the conventional cytarabine and daunorubicin regimen (3‐year RFS 27.7%, p < 0.001; and 3‐year OS 56.4%, p = 0.005) 17–19 . We are conducting a prospective clinical trial to confirm the efficacy of this regimen in patients with CEBPA dm AML (NCT04415008 at http://www.clinicaltrials.gov).…”

Section: Introductionmentioning

confidence: 94%

“…Our previous studies found that the induction regimen including both homoharringtonine and intermediatedose cytarabine produced more favorable outcomes in AML patients with CEBPA dm with 3-year RFS and OS at 84.7% and 92.8%, respectively, compared to the conventional cytarabine and daunorubicin regimen (3-year RFS 27.7%, p < 0.001; and 3-year OS 56.4%, p = 0.005). [17][18][19] We are conducting a prospective clinical trial to confirm the efficacy of this regimen in patients with CEBPA dm AML (NCT04415008 at www.clinicaltrials.gov). Other studies have shown that venetoclax in combination with a hypomethylating agent increased response rates for these patients, especially for older patients.…”

Section: Induction Therapies Affect the Clinical Outcomes Of Aml Withmentioning

confidence: 99%

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Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Liu

Liao

Yang

et al. 2023

Int J Lab Hematology

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IntroductionAcute myeloid leukemia (AML) patients with CEBPA double mutation (CEBPAdm) were associated with distinct immunophenotypes and prognosis. Recently, both International Consensus Classification (ICC) and World Health Organization (WHO) classifications incorporated BZIP single mutations (CEBPAsmBZIP) into the favorable risk group. However, the immunophenotypes of CEBPAsmBZIP mutations have not been characterized, especially when compared with the immunophenotypes of CEBPAdm.MethodsRetrospectively, we investigated and compared the immunophenotypes of AML with CEBPA mutations. Randomforest model and XGBoost algorithm were used to set up a scoring system based on the immunophenotypes of those patients.ResultsIn a total of 967 AML patients: 218 were CEBPAdm (198 consisted of mutations in the BZIP region [CEBPAdmBZIP], 20 were double mutations outside BZIP region [CEBPAdm‐woBZIP]), 117 were CEBPAsm (54 CEBPAsmBZIP and 63 were single mutations outside BZIP region [CEBPAsm‐woBZIP]) and the others were wildtype CEBPA (CEBPAwt). Patients with CEBPAdmBZIP, CEBPAdm‐woBZIP and CEBPAsmBZIP shared the distinct immunophenotype of CD7+ CD34+ MPO+ HLA‐DR+ CD19−, in contrast to patients with CEBPAsm‐woBZIP and CEBPAwt who showed reduced expression of CD7, HLA‐DR, MPO, CD34 and a higher expression of CD19. Based on these immunophenotypes, we developed a scoring system to preemptively identify AML with CEBPAsmBZIP and CEBPAdm and validated it internally and externally.ConclusionsAML with CEBPAdmBZIP, CEBPAdm‐woBZIP, and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm‐woBZIP and CEBPAwt AML.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Induction Therapies Affect the Clinical Outcomes Of Aml Withmentioning

confidence: 99%

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Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Liu

Liao

Yang

et al. 2023

Int J Lab Hematology

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“…Accordingly, CEBPA dm AML has been recognized as a separate entity in the 2016 World Health Organization (WHO) Classification (WHO-2016) [ 12 ] and a favorable-risk category in 2017 European LeukemiaNet (ELN) recommendations. Concomitant WT1 mutations or CSF3R mutations helped predict a poor prognosis in patients with CEBPA dm [ 7 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations

Tien,

Yao,

Tsai

et al. 2024

Blood Cancer J.

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Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPAbZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPAbZIP-inf. One hundred and thirteen CEBPAbZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPAbZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPAbZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPAbZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control.

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“…[1][2][3] Initially, CEBPAdm was stratified into favorable risk group. [4][5][6][7] Recently, studies demonstrated that the presence of inframe bZIP mutations of CEBPA was associated with favorable prognosis in newly diagnosed AML 2,8,9 which was updated in the new International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemia. 10 However, CEBPAdm without bZIP region mutation (CEBPAdmnonbZIP) is classified as CEBPA mutated AML in the 5th edition of WHO Classification of Haematolymphoid Tumours 11 but not in ICC classification.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity analysis of the CEBPAdm AML based on bZIP region mutations

Yan

Zhang

et al. 2023

Blood Science

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Patients with double-mutated CEBPA (CEBPAdm) AML were stratified into favorable risk group, however, few studies have investigated the heterogeneity of different CEBPAdm types in detail. In this study, we analyzed 2211 newly diagnosed AML and identified CEBPAdm in 10.8% of the patients. Within the CEBPAdm cohort, 225 of 239 patients (94.14%) presented with bZIP region mutations (CEBPAdmbZIP) while 14 of 239 patients (5.86%) without bZIP region mutation (CEBPAdmnonbZIP). Analysis of the accompanied molecular mutations showed statistically different incidences of GATA2 mutations between the CEBPAdmbZIP group and the CEBPAdmnonbZIP group (30.29% vs 0%). In the analysis of outcomes, patients with CEBPAdmnonbZIP were associated with shorter overall survival (OS) censored at hematopoietic stem cell transplantation (HSCT) during CR1 compared to those with CEBPAdmbZIP (hazard ratio (HR) = 3.132, 95% confidence interval (CI) = 1.229–7.979, P = .017). Refractory or relapsed AML (R/RAML) patients with CEBPAdmnonbZIP were associated with shorter OS compared to those with CEBPAdmbZIP (HR = 2.881, 95% CI = 1.021–8.131, P = .046). Taken together, AML with CEBPAdmbZIP and CEBPAdmnonbZIP showed different outcomes and might be regarded as distinctive AML entities.

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The prognostic factors in acute myeloid leukaemia with double‐mutated CCAAT/enhancer‐binding protein alpha (CEBPAdm)

Cited by 5 publications

References 19 publications

Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Dysregulated immune and metabolic pathways are associated with poor survival in adult acute myeloid leukemia with CEBPA bZIP in-frame mutations

Heterogeneity analysis of the CEBPAdm AML based on bZIP region mutations

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