Sex chromosome loss may represent a disease‐associated clonal population in chronic lymphocytic leukemia

Chapiro, Élise; Antony-Debré, Iléana; Marchay, Nathalie; Parizot, Christophe; Lesty, Claude; Cung, Hong-Anh; Mathis, Stéphanie; Grelier, Aurore; Maloum, Karim; Choquet, Sylvain; Azgui, Zahia; Uzunov, Madalina; Leblond, Véronique; Merle‐Béral, Hélène; Sutton, Laurent; Davi, Frédéric; Nguyen‐Khac, Florence

doi:10.1002/gcc.22134

Cited by 23 publications

(19 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clonality of T‐lymphocytes could not be convincingly verified in MDS and T‐lymphocytes where therefore excluded to be involved in the clonal process of MDS (Boultwood and Wainscoat, ). Recently, analysis of CD19+ B‐cells and CD3+ T‐cells of CLL patients showed a significantly higher proportion of B‐cells with sex chromosome loss than T‐cells (Chapiro et al, ). However, the conclusion that sex chromosome loss may be a clonal aberration in CLL needs independent confirmation.…”

Section: Discussionmentioning

confidence: 99%

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

Ganster

Kämpfe

Jung

et al. 2015

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

show abstract

Section: Discussionmentioning

confidence: 99%

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

Ganster

Kämpfe

Jung

et al. 2015

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…Some reports describe associations with LOY and worse prognosis in leukemias such as acute myelogenous leukemia (AML) (Holmes et al 1985), cronic myeloid leukemia (CML) (Lippert et al 2010), and chronic lymfocytic leukemia (CLL) (Chapiro et al 2014). In other reports, the prognostic association of LOY for survival in hematologic disease such as myelodysplastic syndrome (MDS) appears to be neutral or even favorable (Wiktor et al 2000).…”

Section: Loy In Blood Cells and Risk For Diseasementioning

confidence: 99%

“…The studies discussed above describe associations between LOY in blood cells and increased risk for various diseases (Holmes et al 1985; Lippert et al 2010; Persani et al 2012; Lleo et al 2013; Chapiro et al 2014; Forsberg et al 2014; Ganster et al 2015; Dumanski et al 2016; Noveski et al 2016; Zhou et al 2016). A critical question to address is how could LOY affecting non-cancerous cells in the peripheral blood can be associated with disease processes in other organs, such as neoplastic proliferation of cells leading to tumors in other organs or neurodegenerative processes in the central nervous system?…”

Section: Loy In Blood Cells Associated With Disease Processes In Othementioning

confidence: 99%

Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

2017

View full text Add to dashboard Cite

Recent discoveries have shown that harboring cells without the Y chromosome in the peripheral blood is associated with increased risk for all-cause mortality and disease such as different forms of cancer, Alzheimer’s disease, as well as other conditions in aging men. In the entire world, the life expectancy of men is shorter compared to women, a sex difference that has been known for centuries, but the underlying mechanism(s) are not well understood. As a male-specific genetic risk factor, an increased risk for pathology and mortality associated with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that men on average live shorter lives compared to women. This review primarily focuses on observed associations between LOY in blood and various diseases in aging men. Other topics covered are known risk factors for LOY, methods to detect LOY, and a discussion regarding mechanisms such as immunosurveillance, that could possibly explain how an acquired mutation in blood cells can be associated with disease processes in other organs.

show abstract

“…However, LOS is typically observed in clonal populations, which further suggests that this cytogenetic aberration is favored for oncogenesis [19]. These findings, along with the fact that hematological malignancies are rarely associated with Turner syndrome, indicate that LOS may not be sufficient for malignant transformation, but is likely to serve as a cooperating event [7, 20].…”

Section: Loss Of a Sex Chromosome (Los) In Hematological Malignanciesmentioning

confidence: 99%

Sex chromosome loss and the pseudoautosomal region genes in hematological malignancies

2016

View full text Add to dashboard Cite

Cytogenetic aberrations, such as chromosomal translocations, aneuploidy, and amplifications, are frequently detected in hematological malignancies. For many of the common autosomal aberrations, the mechanisms underlying their roles in cancer development have been well-characterized. On the contrary, although loss of a sex chromosome is observed in a broad range of hematological malignancies, how it cooperates in disease development is less understood. Nevertheless, it has been postulated that tumor suppressor genes reside on the sex chromosomes. Although the X and Y sex chromosomes are highly divergent, the pseudoautosomal regions are homologous between both chromosomes. Here, we review what is currently known about the pseudoautosomal region genes in the hematological system. Additionally, we discuss implications for haploinsufficiency of critical pseudoautosomal region sex chromosome genes, driven by sex chromosome loss, in promoting hematological malignancies. Because mechanistic studies on disease development rely heavily on murine models, we also discuss the challenges and caveats of existing models, and propose alternatives for examining the involvement of pseudoautosomal region genes and loss of a sex chromosome in vivo. With the widespread detection of loss of a sex chromosome in different hematological malignances, the elucidation of the role of pseudoautosomal region genes in the development and progression of these diseases would be invaluable to the field.

show abstract

Sex chromosome loss may represent a disease‐associated clonal population in chronic lymphocytic leukemia

Cited by 23 publications

References 17 publications

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

New data shed light on Y‐loss‐related pathogenesis in myelodysplastic syndromes

Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men

Sex chromosome loss and the pseudoautosomal region genes in hematological malignancies

Contact Info

Product

Resources

About