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ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype.

ABSTRACT: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML-MRC and 46 controls with acute myeloid leukemia without other specifications (AML-NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated with ASXL1 mutational status. Mutated ASXL1 (ASXL1+) was observed in 31% of patients with AML-MRC compared to 4.3% in AML-NOS. Its presence in AML-MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow, myelomonocytic/monocytic morphological features and normal karyotype. ASXL1 mutation was not observed in patients with myelodysplastic syndrome-related cytogenetic abnormalities or TP53 mutations. Differences in terms of overall survival were found only in AML-MRC patients without prior MDS or MDS/MPN and with intermediate-risk karyotype, having ASXL1+ patients a worst outcome than ASXL1-. We conclude that the ASXL1 mutation frequency is high in AML-MRC patients being its presence associated with specific characteristics including morphological signs of dysplasia. This association raises the possible role of ASXL1 as a surrogate marker in AML-MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML-MRC with intermediate-risk karyotype.

SUBMITTER: Prats-Martin C

PROVIDER: S-EPMC7286456 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype.

Prats-Martín Concepción C Burillo-Sanz Sergio S Morales-Camacho Rosario M RM Pérez-López Olga O Suito Milagros M Vargas Maria T MT Caballero-Velázquez Teresa T Carrillo-Cruz Estrella E González José J Bernal Ricardo R Pérez-Simón José A JA

Cancer medicine 20200326 11

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency of ASXL1 mutations have been described in this leukemia. We sequenced ASXL1 gene mutations in 61 patients with AML-MRC and 46 controls with acute myeloid leukemia without other specifications (AML-NOS) to identify clinical, cytomorphologic, and cytogeneti ...[more]

PMID: 32216059

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Project description:Acute myeloid leukemia with normal karyotype (NK-AML) is a group of diseases with high heterogeneity and immunological processes are significantly associated with its initiation and development. The implication of the immunogenomic landscape in the prognosis of patients with NK-AML has remained largely elusive. In the present study, the expression profiles of immune-related genes (IRGs) were examined and their association with overall survival (OS) was determined in 60 patients with NK-AML from The Cancer Genome Atlas dataset and 104 patients from the Gene Expression Omnibus (GEO) dataset no. GSE71014. Univariate Cox regression analysis was used to identify 42 and 203 IRGs in the two respective cohorts, which were significantly associated with OS in NK-AML. A risk model was constructed based on the regression coefficient and expression values of nine survival-associated IRGs shared between the two datasets [zinc finger CCCH-type containing, antiviral 1 like; transferrin receptor; suppressor of cytokine signaling 1; ELAV like RNA binding protein 1; roundabout guidance receptor 3; unc-93 homolog B1, Toll-like receptor signaling regulator; protein tyrosine phosphatase non-receptor type 6; interleukin 2 receptor subunit alpha (IL2RA) and IL3RA]. Using this risk model, patients with NK-AML may be divided into high- and low-risk groups in prognostic predictions. The area under the receiver operating characteristic curve for predicting OS was 0.793. The prognostic role of this risk model was successfully verified in another independent cohort (GEO dataset no. GSE71014). The prognostic risk score was positively associated with age and fms related receptor tyrosine kinase 3 mutation and correlated with infiltration by T regulatory cells. In conclusion, the results of the present study provided an IRG score model for prognostic stratification of adult patients with NK-AML, as well as further insight into the implication of IRGs in NK-AML that may lead to the development of novel immunotherapy approaches for this disease.

Dataset Information

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype.

Publications

ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia-related changes and normal karyotype.

Similar Datasets

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