MDS-439: A Simplified Three-Marker Panel for Myelodysplastic Syndrome Prognostic Outperforms the Well-Established Revised International Prognostic Scoring Systems (IPSS-R)

The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification model was investigated to distinguish the distinct subclasses of pediatric and adult leukemia, as well as MDS. Overall, the accuracy of the diagnostic classification model for subtyping leukemia was approximately 93%, but this was not reflected for the MDS samples giving only approximately 50% accuracy. Discordant samples of MDS were classified either into acute myeloid leukemia (AML) or “none-of-the-targets” (neither leukemia nor MDS) categories. To clarify the discordant results, all submitted 174 MDS samples were externally reviewed, although this did not improve the molecular classification results. However, a significant correlation was noted between the AML and “none-of-the-targets” categories and prognosis, leading to a prognostic classification model to predict for time-dependent probability of leukemic transformation. The prognostic classification model accurately discriminated patients with a rapid transformation to AML within 18 months from those with more indolent disease.

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Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome?

Journal of Medical Biochemistry ◽

10.2478/jomb-2019-0050 ◽

2019 ◽

Vol 0 (0) ◽

Author(s):

Mehmet Ali Ucar ◽

Anıl Tombak ◽

Simten Dagdas ◽

Aydan Akdeniz ◽

Funda Ceran ◽

...

Keyword(s):

Risk Factors ◽

Myelodysplastic Syndrome ◽

Cox Regression ◽

Bone Marrow Aspiration ◽

Scoring Systems ◽

Control Group ◽

Total Thiol ◽

Healthy Control ◽

Prognostic Scoring Systems ◽

Relationship Of

Summary Background This study planned to investigate the relationship of dynamic thiol/disulfide homeostasis with the prognosis of myelodysplastic syndrome (MDS). Methods 80 patients who had been diagnosed with MDS between 2012 and 2017 and who were older than 18 were included in the study together with 80 healthy control subjects. The MDS diagnosis was confirmed using bone marrow aspiration-biopsy immunostaining. Dynamic thiol/disulfide homeostasis and ischemia-modified albumin (IMA) levels were examined. Results The average IMA (0.71±0.08 vs. 0.67±0.09; p=0.002), median disulfide (18.0 vs. 11.6; p<0.001), median disulfide/native thiol (6 vs. 3; p<0.001), and median disulfide/total thiol (5.4 vs. 2.9; p<0.001) were found higher in the MDS patients compared to control group, and the median hemoglobin, median white blood cell count, median neutrophil count, median lymphocyte count, average native thiol (290.7±48.5 vs. 371.5±103.8; p<0.001), average total thiol (328.2±48.9 vs. 393±105.5; p<0.001), and average native thiol/total thiol (%) (88.3±4.3 vs. 94.2±2.1; p<0.001) were found to be low. Risk factors such as collagen tissue disease (HR:9.17; p=0.005), MDS-EB-1 (HR:10.14; p=0.032), MDS-EB-2 (HR:18.2; p=0.043), and disulfide/native thiol (HR:1.17; p=0.023) were found as the independent predictors anticipating progression to acute myeloid leukemia. In the Cox regression model, risk factors such as age (HR:1.05; p=0.002), MDS-EB-1 (HR:12.58; p<0.001), MDS-EB-2 (HR:5.75; p=0.033), disulfide/native thiol (HR:1.14; p=0.040), and hemoglobin (HR:0.64; p=0.007) were found as predictors anticipating for mortality. Conclusions We can argue that dynamic thiol/disulfide homeostasis could have significant effects on both the etiopathogenesis and the survival of patients with MDS, and it could be included in new prognostic scoring systems.

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