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Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan–Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3β pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS), which are clonal bone marrow malignancies characterized by ineffective hematopoiesis, incorporate a variety of disorders and have variable prognosis. Although the International Prognostic Scoring System (IPSS) provides a clinical model for risk stratification of patients with primary MDS, notable variability in prognosis is still observed within the same IPSS category. Hypoxia-inducible factor-1α (HIF-1α) is associated with an adverse prognosis in patients with solid tumors and some hematological malignancies. However, the relationship between HIF-1α and clinical outcomes of patients with MDS is unknown. We examined HIF-1α by immunohistochemistry in bone marrow specimens from 81 patients with MDS. Results showed that the expression rate of HIF-1α was 49.4% (40/81). Multivariate analysis including age, bone marrow blast percentage, cytogenetics, hemoglobin, white blood cell count and IPSS score demonstrated that HIF-1α ( p = 0.049, HR = 2.704) was an independent prognostic indicator for MDS. Furthermore, the expression of HIF-1α was correlated with poor overall survival ( p < 0.001) and disease progression ( p = 0.004). In addition, correlation analysis revealed that the expression of HIF-1α was associated with bone marrow blast percentage ( p < 0.001, r = 0.510), hemoglobin count (p < 0.001, r = 0.649) and cytogenetics (p = 0.009, r = 0.287). We also found that decitabine achieved a better therapeutic effect compared to traditional chemotherapy in HIF-1α positive patients. In conclusion, these results suggest that HIF-1α is a vital biomarker for predicting the progression and prognosis of MDS. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the arsenic trioxide which can improve the prognosis in adult patients with acute promyelocytic leukemia (APL)carrying ider(17)(q10)t(15:17) that shows poor response to all-trans retinoic acid (ATRA).

Summary: As reported, SETD2 is recurrently mutated in acute myeloid leukaemia (AML), but knowledge about the specifics is limited. We enrolled 530 consecutive newly diagnosed AML patients in our study, and we analysed the distribution pattern and prognostic role of SETD2 mutation in AML. SETD2 mutation was found to affect 6.3% of AML patients, and it frequently co‐occurred with IDH2, NRAS and CEBPA mutations. SETD2‐mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2‐mutated patients who have additional mutations, such as NRAS mutation. [ABSTRACT FROM AUTHOR]

This study included 146 primary gastric diffuse large B-cell lymphoma patients. Next-generation RNA sequencing and fluorescent in situ hybridization were performed on tumors from 27 and 38 patients, respectively. Five-year and 10-year overall survival (OS) rates were 77% and 57%, respectively. Lugano and TNM clinical stage were independent survival factors. Tier I mutation was found in 21 patients. The genetic subtypes were A53 (n = 3), MCD (n = 5), BN2 (n = 5), N1 (n = 5), EZB (n = 1), and NOS (n = 8). OS was significantly shorter in high-risk genetic subtypes (A53, MCD, and N1) than low-risk subtypes (BN2, EZB, and NOS). Frequencies of high-risk genetic subtypes were higher in patients with Lugano stage II/IV and TNM clinical stage III + IV than in those with Lugano stage I and TNM clinical stage I + II. Although genetic testing was performed in only a small number of cases, the results suggested that high-risk genetic subtypes were associated with advanced clinical stages and shorter survival. [ABSTRACT FROM AUTHOR]

Background: The implication of mutational variant allelic frequency (VAF) has been increasingly considered in the prognostic interpretation of molecular data in myeloid malignancies. However, the impact of VAF on outcomes of myelodysplastic syndromes (MDS) has not been extensively explored. Methods: Targeted next-generation sequencing was performed in 350 newly diagnosed MDS cases. The associations of mutational VAF of each gene with overall survival (OS) and leukemia-free survival (LFS) were examined by multivariate Cox regression after univariate analysis. Results: Shorter OS was independently associated with DNMT3A VAF (HR 1.020 per 1% VAF increase; 95% CI 1.005–1.035; p = 0.011) and TP53 VAF (HR 1.014 per 1% VAF increase; 95% CI 1.006–1.022; p = 0.001). LFS analyses revealed that TET2 VAF (HR 1.013 per 1% VAF increase; 95% CI 1.005–1.022; p = 0.003) and TP53 VAF (HR 1.012 per 1% VAF increase; 95% CI 1.004–1.021; p = 0.005) were independently associated with faster leukemic transformation. Furthermore, we established nomograms to predict OS and LFS, respectively, by integrating independent mutational predictors into the revised International Prognostic Scoring System. Conclusion: Our study highlights that VAF of certain genes should be incorporated into routine clinical prognostication of survival and leukemic transformation of MDS. [ABSTRACT FROM AUTHOR]

Abstract: Currently, there are few studies that address the prognostic significance of baseline additional chromosomal abnormalities (ACAs) in newly diagnosed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) as the front-line therapy. A series of 271 consecutive APL patients has been cytogenetically investigated between 2004 and 2011 in our institution. The incidence of ACAs was 27% (46/172) in APL cases with t(15;17). Trisomy 8 was the most recurrent abnormality, accounting for 30% (14/46) of patients with ACAs, followed by +21 (7%, 3/46) and −7/7q (7%, 3/46). Nine cases (14.1%) were found to have additional balanced translocation aberrations, most of them are new and non-recurrent. Treatment protocols consisted of all-trans retinoic acid (ATRA) and chemotherapy with or without the ATO therapy. Overall, patients with and without ACAs had similar complete remission (CR) rates (94% and 98%, respectively, P =0.344). With a median follow-up of 41 months, univariate analysis showed that ACAs did not show any prognostic significance in relapse-free survival (RFS) and overall survival (OS). In addition, ATO treatment was an independent favorable predictor for RFS. Thus, this data provides insights into cytogenetic features of APL, and suggests that ATO-based combination therapy improved RFS in de novo APL patients, while ACAs had no impact on prognosis. [Copyright &y& Elsevier]

Aim: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). Methods: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy‐three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next‐generation sequencing. Genetic and biological features and their association with survival were evaluated. Results: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1‐16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9‐12.8) than those with non‐vCK (16.1 months with 95% CI 11.5‐20.8) (P =.02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5‐11.5 vs 26.1 months with 95% CI 8.0‐44.2, P <.01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild‐type TP53 (60% vs 22.2%, P =.03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P =.03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. Conclusions: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract: Musashi-2 (MSI2) expression of 116 adult B-cells acute lymphoblastic leukemia (B-ALL) patients was measured by real-time PCR. Kaplan–Meier analysis showed that patients with high MSI2 expression had inferior overall survival (OS) (P =0.004), event free survival (EFS) (P =0.001) and relapse free survival (RFS) (P =0.018) in BCR-ABL-negative B-ALL. Multivariate models revealed that, besides WBC more than 30×109/L and IK6 variant of IKZF1, high MSI2 expression was also an independent prognostic factor for adult BCR-ABL-negative B-ALL. Our data suggest that high MSI2 expression could indicate poor prognosis and facilitate risk and treatment stratification in adult BCR-ABL-negative B-ALL. [Copyright &y& Elsevier]