Ling Pan

Potential role of exosome-associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma

Multiple myeloma (MM) is the second most common hematologic neoplasms and an appropriate in vivo environment for myeloma cells has potential implications for initiation, progression, and metastasis of MM. Exosomes, entities carrying microRNAs (miRNAs) to target locations, participate in the cross-talk between myeloma cells and nonmalignant components of the in vivo environment. This study disclosed the emerging roles of circulating exosome-associated miRNAs in drug resistance (DR) of MM. To this end, the medical records of consecutively hospitalized MM patients, who received novel agents-based therapies, were analyzed. Then, an optimized procedure was established for exosome isolation and exosomal RNA analysis. The exosome-associated miRNA expression patterns for predicting bortezomib (Bz) resistance of MM were further examined using a microarray. In total, 204 patients were enrolled with DR rates of 36.5%, 73.1% and 81.8% in the bortezomib (Bz), thalidomide and lenalidomide containing groups. The serum total light chain ratio ≥ 100, CRP ≥ 20 mg/L, and the second-line usage increased risks of acquired Bz-resistance. Among 68 cases having genetic tests, a high risk factor for predicting de novo DR was 1q21 amplification, which also correlated with lower levels of cholesterol and LDL-C. Moreover, nano-sized exosomes were isolated with significantly increasing internal RNAs and down-regulation of exosomal miR-16-5p, miR-15a-5p and miR-20a-5p, miR-17-5p was revealed in the patients resistant to Bz. The routine workup of MM hardly suggested a value for DR prediction. The circulating exosomes carrying miRNAs provided a window that permits a better understanding of the in vivo intercellular crosstalk in MM patients.

Sustaining integrating imatinib and interferon-α into maintenance therapy improves survival of patients with Philadelphia positive acute lymphoblastic leukemia ineligible for allogeneic stem cell transplantation

Abstract We report the clinical results of sustainedly integrating imatinib and interferon-α into maintenance therapy in the patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Maintenance therapy lasted for 5 years with imatinib 400 mg daily, interferon-α 3 million units, 2∼3 doses per week, and chemotherapy including vindesine and dexamethasone scheduled monthly in first year, once every 2 months in second year, and once every 3 months in third year. The chemotherapy was discontinued after 3 years and the imatinib and interferon-α continued for another 2 years. For 41 patients without allo-HSCT with a median follow-up of 32 months, the 3-year DFS and OS were 42.7  ± 8.6% and 57.9  ± 8.4%, respectively. Our study suggests that sustaining maintenance with low-dose chemotherapy, imatinib and interferon-α improved survival of adult Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients ineligible for allo-HSCT, and even provided an opportunity for cure. BCR/ABL persistent negativity at 6 and 9 months may have benefit to choose suitable patients for the imatinib/interferon-α maintenance strategy.

Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 ( UBE2E1 ) as a prognostic factor in acute myeloid leukemia

BackgroundPrevious research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions.MethodsWe performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis.ResultsMicroarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p < 0.05). Next, we validated our findings in an independent cohort of AML samples collected in our hospital. We found that ubiquitin-conjugating enzyme E2E1 (UBE2E1) expression was adversely correlated with AML survival (p = 0.04). Multivariable analysis showed that UBE2E1high patients had a significant shorter OS and shorter progression-free survival after adjusting other known prognostic factors (p = 0.03). At last, we found that UBE2E1 expression was negatively correlated with patients’ response to induction chemotherapy (p < 0.05).ConclusionsIn summary, we demonstrated that UBE2E1 expression was a novel prognostic factor in adult, non-APL AML patients.

CD30 expression and survival in extranodal NK/T-cell lymphoma: a systematic review and meta-analysis

Background The paradoxical reports about the prognostic value of the CD30 expression in extranodal NK/T-cell lymphoma (ENKTL) have restricted its further applications in clinical practice. To identify the common effects and the variation, we conducted this systematic review and meta-analysis. Methods PubMed, MEDLINE, Embase, and Web of Science were searched between January 1975 and 31 January 2017. The pooled hazard ratio was used to estimate the effect of the CD30 expression on overall survival. Bias was assessed by prespecified criteria referring to Reporting Recommendations for Tumor Marker Prognostic Studies and Newcastle-Ottawa Scale. Results Ten retrospective cohort studies with 310 patients are included. CD30 is associated with better overall survival significantly (HR 0.71, 95% CI 0.51 to 0.99, I2 = 0%). A greater effect is observed among studies including participants predominant in regional involvement (HR 0.31, 95%CI 0.13 to 0.76, I2 = 0%) compared with those in systemic involvement. Conclusions This study indicates that the CD30 expression is significantly associated with better prognosis in ENKTL, especially for patients with regional lymphoma involvement.