Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal hematopoietic stem cell diseases. MDS is characterized by dysplasias, cytopenias and an increased risk of acute myeloid leukemia (AML) evolution. MDS has a higher incidence in elderly patients, and is rare in pediatric patients. Cytogenetic analysis is an important laboratory tool for diagnosis, prognosis and clinical decision-making for MDS patients. Chromosome alterations can be detected in 30-50% in MDS. The most frequent chromosomal abnormalities are: del(5q), del(7q)/-7, +8, del(11q), del(12p), del(17p), del(20q) - Y. Rare cytogenetic abnormalities usually are considered as intermediate group in the Revised International Prognostic Scoring System (IPSS-R), as the cytogenetic biclonal abnormalities. However, this group of chromosomal abnormalities may be reported to help to elucidate its clinical implications in de novo MDS. The aim of this study was to report rare cases of cytogenetic biclonal alterations in pediatric and adult patients with de novo MDS and their clinical implications.

This study included 7 patients with MDS, being 3 pediatric patients and 4 adult patients from a cohort of 1056 de novo MDS patients. Chromosomal and clinical studies were carried out in 1056 MDS patients, being 200 pediatric patients and 856 adult patients, between 2000-2022. Cytogenetic analyses were performed in bone marrow cells by G-banding and fluorescence in situ hybridization (FISH).

A total of 7 (0.66%) patients with de novo MDS (7/1056) had biclonal cytogenetic abnormalities, being 4 (0.48%) adult patients (4/856), and 3 (1.5%) pediatric patients (3/200). The mean age of adult patients was 67.5 (60-73 years old), and pediatric patients were 10 (6-13 years old). Most of the patients (57%) were classified as advanced stages (MDS-EB-1, MDS-EB-2 and MDS-EB-t) and dysplasias in more than one lineage (71%). The cytogenetic biclonality in adult patients involved the clones with the chromosomal alterations: del(11q),del(20q)/del(12p); Y/del(17p); del(11q),+21/del(6q); i(17q)/hyperdiploidy karyotype; and in pediatric patients del(17p)/del(12p); +X,+8/add(7p); +8/+21.

Biclonal cytogenetic alterations are uncommon findings, with a frequency between 1.6%-6.5% in MDS. Although we studied a large cohort of MDS patients the frequency of these alterations was lower than literature (0.66%). It is important to note that most studies included secondary or therapy-related MDS and AML which generally have a higher chromosomal instability. In our results, the chromosomal instability in these clones involved common cytogenetic alterations: del(11q), del(12p), del(17p) and +8, but the prognostic value of this distinct cytogenetic clones still needs to be elucidated. The mechanisms for the development of unrelated cytogenetic clones remain to be elucidated, especially because it is unclear if these clones are in fact two independent clones, representing a true biclonality, or a clonal evolution derived from a common precursor with a submicroscopic molecular genetic change.

Our study shows new insights into biclonal cytogenetic abnormalities in de novo MDS, demonstrating for the first time, from a large cohort of de novo MDS patients, the frequency of cytogenetic biclonality in pediatric and adult patients.