Intriguingly, in eight of the nine (88.9%) MDS-F cases with elevated NESCs, a majority of NESCs also expressed GFAP, with an additional increase in GFAP single-positive cells.
Multivariate analysis showed diagnosis was the independent risk factor for antibodies, as acute lymphoblastic leukemia (ALL) patients (HR0.141, 95% CI: 0.037-0.538, p = 0.004) had a lower incidence of class II PRAs and DSAs against HLA-B, DQ, and DR, whereas myelodysplastic syndrome (MDS) patients had a higher incidence of PRAs for both class I and class II (HR4.790, 95% CI: 1.010-22.716, p = 0.049), and DSAs against HLA-A, B, C, DP, and DQ.
In addition, the expression of BCAS4, ADA, and YWHAB genes was significantly reduced in MDS patients without chromosome 20 abnormalities, which suggests that these three genes were commonly involved in the molecular pathogenesis of MDS.
We previously reported that the expression of serine protease inhibitor kunitz-type2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, is significantly lower in BMMSC from myelodysplastic syndromes (MDS) patients compared to healthy donors (HD).
In the validation cohort, only a polymorphism in MLH1 was significantly associated with development of MDS in patients with poor cytogenetics (p = 0.0004).
Stimuli provided by MDS-MSCs impaired the growth and function of healthy HSPCs, which is further sustained autonomously in HSPCs for significant periods of time resulting in a failure for active hematopoietic engraftment across primary and secondary transplant recipients (chimerism: 0.34-91% vs 2.78%, engraftment frequencies: at 0.06 ± 0.02 vs full engraftment for MDS-MSC vs healthy groups, respectively).
Collectively, mutations in U2AF1 induce expression of therapeutically targetable 'active' IRAK4 isoforms and provide a genetic link to activation of chronic innate immune signalling in MDS and AML.
Silencing NRF2 or dual specificity protein phosphatase 1 also significantly sensitized cytarabine treatment and inhibited tumors in MDS cells transplanted mouse models <i>in vivo</i> Our study suggests that targeting NRF2 in combination with conventional chemotherapy could pave the way for future therapy for high-risk MDS.
In summary, our results indicate that a familial MDS-associated HLTFE259K germline mutation induces accumulation of DNA double-strand breaks, possibly through impaired PCNA polyubiquitination.
Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS.
Through assessment of patient gene expression, we have identified STK4 (encoding Hippo kinase MST1) as a 20q gene that is downregulated below haploinsufficient amounts in myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN).
Incorporating the revised International Prognostic Scoring System classification with the ACE-27 and TP53 mutation status improved outcome prediction in patients with MDS.
Anemia of lower-risk myelodysplastic syndromes (MDSs) and primary myelofibrosis (PMF) generally becomes resistant to available treatments, leading to red blood cell (RBC) transfusions, iron overload, shortened survival, and poor quality of life.
In the screening cohort, 6 candidate SNPs were associated with the tendency to develop MDS: rs4135113 (TDG, p = 0.03), rs12917 (MGMT, p = 0.003), rs2230641 (CCNH, p = 0.01), rs2228529 and rs2228526 (ERCC6, p = 0.04 and p = 0.03), and rs1799977 (MLH1, p = 0.04).
In our previous study, we identified fusion of the additional sex combs-like 1 (ASXL1) and teashirt zinc finger homeobox 2 genes in a patient with myelodysplastic syndrome.
This study included patients with IPSS lower-risk MDS from the DRAMA (An Observational Study for Dacogen Long-Term Treatment in Patients With Myelodysplastic Syndrome; NCT01400633) and DIVA (A Study for Dacogen Treatment in Patients With Myelodysplastic Syndrome; NCT01041846) studies, which were prospective observational studies on the efficacy and safety of decitabine treatment in patients with MDS.
Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance.
MDS-MSCs that fail to respond to hypomethylating therapy are associated with patients with rapid adverse disease transformation and this further suggests that MDS-MSCs may be an integral part of disease progression and have prognostic value as well as potential as a therapeutic target.
We previously reported that the expression of serine protease inhibitor kunitz-type2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, is significantly lower in BMMSC from myelodysplastic syndromes (MDS) patients compared to healthy donors (HD).