Emergence and Cytogenetic Clonal Evolution of Chromosome 7 Abnormalities in Myeloid Malignancies: Investigating the Role of Telomere Dysfunction

TL;DR

This study explores how chromosome 7 abnormalities in myeloid cancers may develop due to telomere dysfunction, offering insights into disease progression and treatment strategies.

Contribution

The study introduces the concept of cytogenetic clonal evolution of chromosome 7 abnormalities (CCE7) and links it to telomere dysfunction.

Findings

CCE7 is associated with disease progression and can evolve into monosomy 7.

Telomere loss or shortening contributes to chromosomal instability and unstable chromosome 7 derivatives.

Variants in telomere-related genes are linked to specific chromosome 7 abnormalities.

Abstract

Monosomy 7 and deletion 7q are common chromosomal abnormalities in myeloid malignancies, and they are associated with a poor prognosis. The mechanism underlying their acquisition remains elusive. We identified a cohort of 24 patients exhibiting clones with different chromosome 7 abnormalities, such as deletion 7q, unstable derivatives (ring chromosomes or ‘naked’ centromeres), and monosomy 7. We designated this group as having cytogenetic clonal evolution of chromosome 7 abnormalities (CCE7). In some cases, CCE7 correlated with disease progression, suggesting that deletions or other derivatives involving the q-arm of chromosome 7 may arise early in the disease course. These abnormalities may be transient but can potentially evolve into monosomy 7. Within the CCE7 group, telomere loss or shortening may contribute to chromosomal instability and the emergence of unstable derivatives, as the chromosome 7 derivatives displayed loss or rearrangement of subtelomeric regions. Moreover, we identified variants in genes implicated in telomere biology disorders and observed specific genetic mutation profiles associated with different chromosome 7 abnormalities. These findings shed light on a potential mechanism leading to monosomy 7 through the evolution of chromosome 7q abnormalities. Identifying patients at risk of developing monosomy 7, based on the presence of unstable derivatives with telomere loss or a specific mutation profile, could potentially enhance patient management and guide the development of novel therapeutic strategies.

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