Limits...
Distinct clinical and experimental characteristics in the patients younger than 60 years old with myelodysplastic syndromes.

Li X, Xiao ZJ, Chang CK, Xu F, Wu LY, He Q, Xu ZF, Song LX, Zhang Z, Zhou LY, Su JY, Zhang X, Guo J - PLoS ONE (2013)

Bottom Line: However, MDS is commonly found in young individuals (<60 years) in Asia.Obvious amplification of T cells and low CFU formation could be found in the younger patients.CFU formation was significantly increased in the younger patients after the removal of activated T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Sixth Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. lixiao3326@yahoo.com.cn

ABSTRACT
Myelodysplastic syndromes (MDS) mainly occur in elderly individuals in Western countries. However, MDS is commonly found in young individuals (<60 years) in Asia. The reason for the high incidence in younger individuals is still unclear, and the differences in disease features between young and elderly patients with MDS have been not well recognized. To explore these issues, in this study, we analyzed the clinical and experimental characteristics of MDS in the patients younger and older than 60 years old and characterized the potential age-associated differences. The results showed that over half of the patients with MDS (61.9%) were younger than 60 years old upon the first diagnosis. The younger patients were more likely to be female, who have lower risk and less advanced MDS. The occurrence of trisomy 8 and bone marrow failure were more frequent in the younger patients than the older ones. The marrow CD34+ cells in the younger patients showed lower proliferation and higher apoptosis in comparison with that in the older ones. Obvious amplification of T cells and low CFU formation could be found in the younger patients. CFU formation was significantly increased in the younger patients after the removal of activated T cells. In addition, the younger patients had a lower frequency of p15(INK4B) methylation, longer survival expectancy and less AML transformation. In summary, the younger patients with MDS in China may show more benign disease features than the older ones. Enhanced immunological response may be involved in the pathogenesis of MDS in the patients younger than 60 years.

Show MeSH

Related in: MedlinePlus

(A) Possible pathogenesis in younger patients; (B) Possible pathogenesis in older patients.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585386&req=5

pone-0057392-g005: (A) Possible pathogenesis in younger patients; (B) Possible pathogenesis in older patients.

Mentions: These characteristics suggested a trend towards bone marrow failure rather than disease progression for younger patients with MDS. What are the reasons for such distinct features in younger MDS patients? To put in another way, whether these characteristics imply some distinct age-associated pathogenesis in MDS is worth discussing We present the following hypothesis based on our observations (Figure 5). Both the female-to-male ratio and the prevalence of trisomy 8 were much higher in the younger patients than the older ones. It is well known that most autoimmune-related disorders are more commonly observed in females, with several reports indicating that MDS with trisomy 8 is often accompanied by autoimmune diseases, such as Behçet’s disease or adult Still’s disease [30], [31]. 16 patients with MDS were found to have both trisomy 8 and autoimmune diseases (unpublished data). In this study, the younger patients had frequent bone marrow failure and increased CFU growth after removal of the activated T cells in vitro, suggesting that younger MDS patients have a stronger self-immune surveillance reaction during the development and progression of MDS. The formation of initial MDS clones in the younger patients may induced a strong T-cell response, which in turn suppressed the MDS clones but simultaneously resulted in severe BM failure and an autoimmune-like clinical presentation. Lower incidence of abnormal chromosomes and better differentiation of CD34+ cells observed in the younger patients, may contribution to the existence of the initial MDS clones in conditions of strong T-cell attack. The stronger T-cell self-immune surveillance and performance of TSGs function (less p15INK4B methylation) suppressed the development of clonal cells in younger patients, which yielded more low-risk patients, less AML transformation, and ultimately, significantly longer overall survival. On the contrary, the MDS malignant clones in the older patient might not be controlled by the weaker T-cell response (demonstrated by the presence of fewer CFUs compared with the younger patients after the deletion of the activated CD4 or CD8 cells) and the activated TSGs, although some of the tumor-targeted T cells (such as Tc1 and NK) number expanded. Predominantly malignant clones such as 5q−/−5 that were more frequently observed in older patients could be selected and expanded preferentially due to the weaker T-cell response in those patients. Weaker T-cell surveillance, poor differentiation of CD34+ cells and frequent activation of TSGs may result in more higher risk diseases, more rapid AML transformation, and ultimately, obviously shorter OS.


Distinct clinical and experimental characteristics in the patients younger than 60 years old with myelodysplastic syndromes.

Li X, Xiao ZJ, Chang CK, Xu F, Wu LY, He Q, Xu ZF, Song LX, Zhang Z, Zhou LY, Su JY, Zhang X, Guo J - PLoS ONE (2013)

(A) Possible pathogenesis in younger patients; (B) Possible pathogenesis in older patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585386&req=5

pone-0057392-g005: (A) Possible pathogenesis in younger patients; (B) Possible pathogenesis in older patients.
Mentions: These characteristics suggested a trend towards bone marrow failure rather than disease progression for younger patients with MDS. What are the reasons for such distinct features in younger MDS patients? To put in another way, whether these characteristics imply some distinct age-associated pathogenesis in MDS is worth discussing We present the following hypothesis based on our observations (Figure 5). Both the female-to-male ratio and the prevalence of trisomy 8 were much higher in the younger patients than the older ones. It is well known that most autoimmune-related disorders are more commonly observed in females, with several reports indicating that MDS with trisomy 8 is often accompanied by autoimmune diseases, such as Behçet’s disease or adult Still’s disease [30], [31]. 16 patients with MDS were found to have both trisomy 8 and autoimmune diseases (unpublished data). In this study, the younger patients had frequent bone marrow failure and increased CFU growth after removal of the activated T cells in vitro, suggesting that younger MDS patients have a stronger self-immune surveillance reaction during the development and progression of MDS. The formation of initial MDS clones in the younger patients may induced a strong T-cell response, which in turn suppressed the MDS clones but simultaneously resulted in severe BM failure and an autoimmune-like clinical presentation. Lower incidence of abnormal chromosomes and better differentiation of CD34+ cells observed in the younger patients, may contribution to the existence of the initial MDS clones in conditions of strong T-cell attack. The stronger T-cell self-immune surveillance and performance of TSGs function (less p15INK4B methylation) suppressed the development of clonal cells in younger patients, which yielded more low-risk patients, less AML transformation, and ultimately, significantly longer overall survival. On the contrary, the MDS malignant clones in the older patient might not be controlled by the weaker T-cell response (demonstrated by the presence of fewer CFUs compared with the younger patients after the deletion of the activated CD4 or CD8 cells) and the activated TSGs, although some of the tumor-targeted T cells (such as Tc1 and NK) number expanded. Predominantly malignant clones such as 5q−/−5 that were more frequently observed in older patients could be selected and expanded preferentially due to the weaker T-cell response in those patients. Weaker T-cell surveillance, poor differentiation of CD34+ cells and frequent activation of TSGs may result in more higher risk diseases, more rapid AML transformation, and ultimately, obviously shorter OS.

Bottom Line: However, MDS is commonly found in young individuals (<60 years) in Asia.Obvious amplification of T cells and low CFU formation could be found in the younger patients.CFU formation was significantly increased in the younger patients after the removal of activated T cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, The Sixth Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. lixiao3326@yahoo.com.cn

ABSTRACT
Myelodysplastic syndromes (MDS) mainly occur in elderly individuals in Western countries. However, MDS is commonly found in young individuals (<60 years) in Asia. The reason for the high incidence in younger individuals is still unclear, and the differences in disease features between young and elderly patients with MDS have been not well recognized. To explore these issues, in this study, we analyzed the clinical and experimental characteristics of MDS in the patients younger and older than 60 years old and characterized the potential age-associated differences. The results showed that over half of the patients with MDS (61.9%) were younger than 60 years old upon the first diagnosis. The younger patients were more likely to be female, who have lower risk and less advanced MDS. The occurrence of trisomy 8 and bone marrow failure were more frequent in the younger patients than the older ones. The marrow CD34+ cells in the younger patients showed lower proliferation and higher apoptosis in comparison with that in the older ones. Obvious amplification of T cells and low CFU formation could be found in the younger patients. CFU formation was significantly increased in the younger patients after the removal of activated T cells. In addition, the younger patients had a lower frequency of p15(INK4B) methylation, longer survival expectancy and less AML transformation. In summary, the younger patients with MDS in China may show more benign disease features than the older ones. Enhanced immunological response may be involved in the pathogenesis of MDS in the patients younger than 60 years.

Show MeSH
Related in: MedlinePlus