Ring sideroblasts in AML are associated with adverse risk characteristics and have a distinct gene expression pattern

Berger, Gerbrig; Gerritsen, M; Yi, Guoqiang; Koorenhof-Scheele, Theresia N.; Kroeze, Leonie I.; Stevens‐Kroef, Marian; Yoshida, Kenichi; Shiraishi, Yuichi; Berg, Eva van den; Schepers, Hein; Huls, G.; Mulder, André B.; Ogawa, Seishi; Martens, Joost H.A.; Jansen, Joop H.; Vellenga, Edo

doi:10.1182/bloodadvances.2019000518

Cited by 6 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, we verified whether the observed findings of mutant p53 in HSPC and cell lines were also present in patient AML cells (which have also additional mutations) with and without TP53 mutations. Therefore, we used three large available data sets (Blueprint [14] supplemented with five additional TP53 mutant AML [15], TCGA [16], and BeatAML [17]) and identified the differentially expressed genes between TP53 mut and TP53 wt AMLs for each database. Per data set, we detected differential gene expression between TP53 mut AMLs and TP53 wt AMLs.…”

Section: Resultsmentioning

confidence: 99%

“…Also, previous studies had revealed an association between TP53 mutations and erythroid development in leukemia. In acute erythroid leukemia, a high incidence of loss of WT TP53 function is noted [21,25], and the presence of ring sideroblasts in secondary AML is frequently associated with TP53 mutations [15].…”

Section: Discussionmentioning

confidence: 99%

“…Differential gene expression of TP53mut AMLs was determined from in-house samples (Blueprint, Supplementary Table E1, online only, available at www.exphem.org) [14,15]. (n = 39, TP53 mut = 6); the TCGA data set [11,16] (n = 179, TP53 mut = 20); and the Bea-tAML data set [17] (n = 494, TP53 mut = 26) [17].…”

Section: Data Retrievalmentioning

confidence: 99%

See 2 more Smart Citations

Presence of mutant p53 increases stem cell frequency and is associated with reduced binding to classic TP53 binding sites in cell lines and primary AMLs

Gerritsen¹,

Hilgendorf²,

Yi³

et al. 2022

Experimental Hematology

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Presence of mutant p53 increases stem cell frequency and is associated with reduced binding to classic TP53 binding sites in cell lines and primary AMLs

Gerritsen¹,

Hilgendorf²,

Yi³

et al. 2022

Experimental Hematology

Self Cite

View full text Add to dashboard Cite

“…The correlation between SF3B1 mutations and the RS phenotype is not as strong as in MDS. RNA sequencing analysis on precursor cells revealed that several heme metabolism-related genes are upregulated in AML-RS cells similarly to SF3B1-mutated MDS, demonstrating the involvement of common downstream effector pathways [53].…”

Section: Sf3b1 In Acute Myeloid Leukemiamentioning

confidence: 98%

SF3B1 Mutations in Hematological Malignancies

Cilloni

Itri

Bonuomo

et al. 2022

Cancers

View full text Add to dashboard Cite

Recently, mutations in the genes involved in the spliceosome have attracted considerable interest in different neoplasms. Among these, SF3B1 mutations have acquired great interest, especially in myelodysplastic syndromes, as they identify a subgroup of patients who can benefit from personalized therapy. The SF3B1 gene encodes the largest subunit of the splicing factor 3b protein complex and is critical for spliceosome assembly and mRNA splicing. The mutated SF3B1 gene encodes for a protein with a different mRNA processing mechanism that results in the aberrant splicing of many mRNAs, which can be downregulated. Although there are many mRNAs affected by a splicing alteration, only a few of these have been directly related to the pathogenesis of several diseases. In this review, we took a snapshot of the current knowledge on the implications of SF3B1 mutations in different hematological malignancies.

show abstract

“…Ring sideroblasts can also be present in a subset of patients with acute myeloid leukemia (AML), ranging from 5 to 16% [ 141 , 189 ], whereas SF3B1 mutations are infrequent [ 141 , 190 ]. Berger et al studied 126 AML patients with ring sideroblasts ≥1% [ 191 ]. AML-RS subjects were enriched in the ELN adverse risk category with 35% of all cases showing cytogenetic aberrancies.…”

Section: Clonal Sideroblastic Anemiasmentioning

confidence: 99%

Causes and Pathophysiology of Acquired Sideroblastic Anemia

Rodríguez‐Sevilla

Calvo

Arenillas

2022

Genes

View full text Add to dashboard Cite

The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by anemia and the presence of ring sideroblasts in the bone marrow. Ring sideroblasts are abnormal erythroblasts with iron-loaded mitochondria that are visualized by Prussian blue staining as a perinuclear ring of green-blue granules. The mechanisms that lead to the ring sideroblast formation are heterogeneous, but in all of them, there is an abnormal deposition of iron in the mitochondria of erythroblasts. Congenital sideroblastic anemias include nonsyndromic and syndromic disorders. Acquired sideroblastic anemias include conditions that range from clonal disorders (myeloid neoplasms as myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms with ring sideroblasts) to toxic or metabolic reversible sideroblastic anemia. In the last 30 years, due to the advances in genomic techniques, a deep knowledge of the pathophysiological mechanisms has been accomplished and the bases for possible targeted treatments have been established. The distinction between the different forms of sideroblastic anemia is based on the study of the characteristics of the anemia, age of diagnosis, clinical manifestations, and the performance of laboratory analysis involving genetic testing in many cases. This review focuses on the differential diagnosis of acquired disorders associated with ring sideroblasts.

show abstract

Ring sideroblasts in AML are associated with adverse risk characteristics and have a distinct gene expression pattern

Abstract: Key Points Ring sideroblasts in AML are associated with complex karyotypes and TP53 mutations. Gene expression studies in CD34+ AML cells suggest an altered erythroid differentiation program in AML with ring sideroblasts.

Cited by 6 publications

References 41 publications

Presence of mutant p53 increases stem cell frequency and is associated with reduced binding to classic TP53 binding sites in cell lines and primary AMLs

Presence of mutant p53 increases stem cell frequency and is associated with reduced binding to classic TP53 binding sites in cell lines and primary AMLs

SF3B1 Mutations in Hematological Malignancies

Causes and Pathophysiology of Acquired Sideroblastic Anemia

Contact Info

Product

Resources

About