From cellular morphology to molecular and epigenetic anomalies of myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDSs) are a myeloid neoplasm with a propensity for natural evolution or transformation to acute leukemias (AL) over time. Mechanisms for MDS transformation to AL remain poorly understood but are related to genomic instability, which affects the production of the different cell lineages. Genomic instability is also generated by dysfunctional telomeres. Indeed telomeres, the protective ends of chromosomes are the backbone of genome stability. Nuclear telomere remodeling is an early indicator of nuclear remodeling preceding the onset of genomic instability and MDS. This review aims to revisit the pathogenesis and pathophysiology of MDS from morphology and cytogenetics to molecular and epigenetic mechanisms. Furthermore, this review will highlight and discuss recent breakthroughs in dysfunctional telomeres and nuclear telomere architecture roles in the pathogenesis and physiopathology of MDS in the global context of genomic instability.

Genetic Landscape of Papillary Thyroid Carcinoma and Nuclear Architecture: An Overview Comparing Pediatric and Adult Populations

“…This gave rise to the hypothesis that re-activated telomerase expression could only allow genetically unstable clones to maintain their telomeres barely above a critically short length, resulting in the prevention of cellular senescence and apoptosis [210]. Telomere shortening, genomic instability, and TERT activation are associated with features of PTC and are the most frequent alterations observed in aggressive stages [211,212]. Therefore, telomere studies could provide additional information to predict metastasis and aggressive behavior of PTC tumors having poor biological characterization and very limited therapeutic options.…”

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

“…Myelodysplastic syndrome (MDS) is a heterogeneous group of hematologic neoplasms classically described as a clonal disorder of hematopoietic stem cells leading to dysplasia and ineffective hematopoiesis in the bone marrow [ 1 ]. Chromosomal abnormalities play an important role in classification and prognostication of MDS patients; however, more than 50% of low-risk MDS patients harbor a normal karyotype as revealed by regular chromosome banding analysis [ 2 , 3 ]. While chromosome banding analysis can only detect gains and/or losses of more than 10 Mb size, it depends on proliferation of the MDS clone to obtain metaphases in vitro.…”

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

“…In MDS, cytogenetic aberrations play an important role in classi cation and prognostication. Chromosomal abnormalities have been detected in approximately 50-60% of MDS patients, including the deletions of chromosome 5q and 7q, trisomy 8, and complex karyotypes [2]. However, more than 50% low risk MDS patients harbor a normal karyotype as revealed by regular chromosome binding analysis but indeed behave with signi cant clinical heterogeneity [3].…”