BackgroundMyelodysplastic syndromes (MDSs) are a very heterogeneous group of myeloid disorders with high prevalence and risk of developing acute myeloid leukemia. The more accurate risk stratification can provide a better guidance of treatment. The platelet–large cell ratio (P-LCR) is a parameter reported in complete blood cell count tests, and was associated with many diseases, but its role in MDS is not clear.PurposeThis study aims to explore the impact of the P-LCR on the prognosis of patients with MDS, which is of great significance for clinical treatment.MethodsIn the retrospective study, 122 newly diagnosed MDS patients were enrolled. We used the bioinformatics tool X-tile to define a P-LCR threshold of 36.7% to predict prognosis. Patients were divided into P-LCRlow and P-LCRhigh groups, and their characteristics were compared between the two groups.ResultsResults show that the P-LCRlow was associated with worse overall survival (OS) than the P-LCRhigh patients (median OS, 18.53 months versus 25.77 months, p=0.0057), but there were no statistical differences in progression-free survival (PFS) between the two groups (p=0.2001). The results of univariate and multivariate Cox proportional hazard analyses adjusted for gender, bone marrow blast level, platelet count, and International Prognostic Scoring System scores showed that the P-LCR was useful in the evaluation of PFS [hazard ratio (HR) 0.212, 95%CI 0.064–0.702, p=0.011] and OS of MDS (HR 0.464, 95%CI 0.284–0.757, p=0.002).ConclusionThis study is the first report showing that the P-LCR would be a simple and immediately available biomarker for predicting the prognosis of MDS.

Background Although B‐acute lymphoblastic leukemia (B‐ALL) patients' survival has been improved dramatically, some cases still relapse. This study aimed to explore the prognosis‐related novel differentially expressed genes (DEGs) for predicting the overall survival (OS) of children and young adults (CAYAs) with B‐ALL and analyze the immune‐related factors contributing to poor prognosis. Methods GSE48558 and GSE79533 from Gene Expression Omnibus (GEO) and clinical sample information and mRNA‐seq from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were retrieved. Prognosis‐related key genes were enrolled to build a Cox proportional model using multivariate Cox regression. Five‐year OS of patients, clinical characteristic relevance and clinical independence were assessed based on the model. The mRNA levels of prognosis‐related genes were validated in our samples and the difference of immune cells composition between high‐risk and low‐risk patients were compared. Results One hundred and twelve DEGs between normal B cells and B‐ALL cells were identified based on GSE datasets. They were mainly participated in protein binding and HIF‐1 signaling pathway. One hundred and eighty‐nine clinical samples were enrolled in the study, both Kaplan–Meier (KM) analysis and univariate Cox regression analysis showed that CYBB, BCL2A1, IFI30, and EFNB1 were associated with prognosis, CYBB, BCL2A1, and EFNB1 were used to construct prognostic risk model. Moreover, compared to clinical indicators, the three‐gene signature was an independent prognostic factor for CAYAs with B‐ALL. Finally, the mRNA levels of CYBB, BCL2A1, and EFNB1 were significantly lower in B‐ALL group as compared to controls. The high‐risk group had a significantly higher percentage of infiltrated immune cells. Conclusion We constructed a novel three‐gene signature with independent prognostic factor for predicting 5‐year OS of CAYAs with B‐ALL. Additionally, we discovered the difference of immune cells composition between high‐risk and low‐risk groups. This study may help to customize individual treatment and improve prognosis of CAYAs with B‐ALL.

Acute myeloid leukemia (AML) with RARG rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four AML with RARG rearrangements were identified. Bleeding or ecchymosis was present at 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of cases, respectively. Immunophenotyping showed following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6 (n=14), NUP98 (n=11), HNRNPc (n=6), HNRNPm (n=1), PML (n=1), and NPM1 (n=1). WT1- and NRAS/KRAS-mutations were common co-mutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (~29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA-seq data from 201 AML patients showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis.