Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by dysplasias, ineffective hematopoiesis and risk of acute myeloid leukemia transformation. Approximately 90% of MDS patients present mutations in genes involved in various cell signaling pathways. Specialized DNA polymerases, such as POLN, POLI, POLK, POLQ, POLH, POLL and REV3L, insert a nucleotide opposite replication–blocking DNA lesions in an error-prone manner and, in this way, sometimes can actively promote the generation of mutation. For the best of our knowledge, has not been described the mutations of these genes in MDS. DNA target sequencing CDS regions of the REV3L gene was performed in a 58-year-old man diagnosed as High Risk Myelodysplastic Syndrome. The patient presented very low hemoglobin, increased number of blasts, karyotype:47,XY,+8[6]/47,XY,del(7)(q32),+8[7], no response to hypomethylating therapy (decitabine), all markers of poor prognosis. Target sequencing identified a mutation c.9253-6T>C REV3L (Substitution - intronic) with VAF (variant allele frequency) = 16% considered pathogenic according to Functional Analysis through. Hidden Markov Models (FATHMM). This is the first evidence of REV3L mutation in MDS and, of utmost importance, associated with poor prognosis.

RESUMO A síndrome mielodisplásica (SMD) é uma desordem clonal das células-tronco hematopoiéticas caracterizada por citopenias periféricas devido à hematopoiese ineficaz e pelo aumento do risco de evolução para a leucemia mieloide aguda (LMA). As alterações cromossômicas representam o marcador mais importante da estratificação de risco para a transformação de LMA. Quebra das cromátides (chtb) é uma descontinuidade de uma única cromátide. Relatamos o caso de um paciente com SMD, cuja análise citogenética mostrou chtb espontâneo: 46,XY,add(13)(q34),chtb(15)(q24)[3]/47,XY,chtb(2)(q22),del(5) (q35),del(7)(q32),+8,del(11q)(q23),del(q22)[cp17]. O paciente foi considerado de alto risco devido ao cariótipo complexo e à presença de chtb. Sugerimos que essa anormalidade cromossômica possa ser considerada como marcador de instabilidade.

ABSTRACT Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by peripheral cytopenias due to ineffective erythropoiesis and an increased risk for evolving into acute myeloid leukemia (AML). Chromosomal abnormalities represent the most important marker of risk stratification for AML transformation. Chromatid break (chtb) is a discontinuity of a single chromatid. We report the case of a patient with MDS whose cytogenetic analysis showed spontaneous chromatid breakage (chrb): 46,XY,add(13)(q34),chtb(15)(q24) [3]/47,XY,chtb(2)(q22),del(5)(q35),del(7)(q32),+8,del(11q)(q23),del(q22)[cp17]. He was considered a high-risk patient due to the complex karyotype and the presence of chtb. We suggest that this chromosomal abnormality may be considered as a marker of genomic instability in MDS.