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CEBPA-IGH, a fusion gene of the immunoglobulin heavy-chain locus (IGH) and the CCAAT enhancer-binding protein α (C/EBPα) gene, is recurrently found in B-ALL cases and causes aberrant expression of C/EBPα, a master regulator of granulocyte differentiation, in B cells. Forced expression of C/EBPα in B cells was reported to cause loss of B-cell identity due to the inhibition of Pax5, a master regulator of B-cell differentiation; however, it is not known whether the same mechanism is applicable for B-ALL development by CEBPA-IGH. It is known that a full-length isoform of C/EBPα, p42, promotes myeloid differentiation, whereas its N-terminal truncated isoform, p30, inhibits myeloid differentiation through the inhibition of p42; however, the differential role between p42 and p30 in ALL development has not been clarified. In the present study, we examined the effect of the expression of p42 and p30 in B cells by performing RNA-seq of mRNA from LCL stably transfected with p42 or p30. Unexpectedly, suppression of PAX5 target genes was barely observed. Instead, both isoforms suppressed the target genes of MEF2 family members (MEF2s), other regulators of B-cell differentiation. Similarly, MEF2s target genes rather than PAX5 target genes were suppressed in CEBP-IGH-positive ALL (n = 8) compared with other B-ALL (n = 315). Furthermore, binding of both isoforms to MEF2s target genes and the reduction of surrounding histone acetylation were observed in ChIP-qPCR. Our data suggest that the inhibition of MEF2s by C/EBPα plays a role in the development of CEBPA-IGH-positive ALL and that both isoforms work co-operatively to achieve it.

The genetic basis of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unclear, and its clinical outcome remains unsatisfactory. This study aimed to advance the understanding of biological characteristics, improve disease stratification, and identify molecular targets of adult B-ALL. Adolescents and young adults (AYA) (15 to 39 years old, n = 193) and adults (40 to 64 years old, n = 161) with Philadelphia chromosome-negative (Ph−) B-ALL were included in this study. Integrated transcriptomic and genetic analyses were used to classify the cohort into defined subtypes. Of the 323 cases included in the RNA sequencing analysis, 278 (86.1%) were classified into 18 subtypes. The ZNF384 subtype (22.6%) was the most prevalent, with 2 novel subtypes (CDX2-high and IDH1/2-mut) identified among cases not assigned to the established subtypes. The CDX2-high subtype (3.4%) was characterized by high expression of CDX2 and recurrent gain of chromosome 1q. The IDH1/2-mut subtype (1.9%) was defined by IDH1 R132C or IDH2 R140Q mutations with specific transcriptional and high-methylation profiles. Both subtypes showed poor prognosis and were considered inferior prognostic factors independent of clinical parameters. Comparison with a previously reported pediatric B-ALL cohort (n = 1003) showed that the frequencies of these subtypes were significantly higher in AYA/adults than in children. We delineated the genetic and transcriptomic landscape of adult B-ALL and identified 2 novel subtypes that predict poor disease outcomes. Our findings highlight the age-dependent distribution of subtypes, which partially accounts for the prognostic differences between adult and pediatric B-ALL.

Rickettsiales-like organisms are important for the survival and functioning of corals, prompting an investigation of their complete genomes. Earlier reports of the genomes of these organisms remain incomplete. Here, we report a novel draft genome of Rickettsiales bacterial strain SESOKO1, found in Acropora tenuis coral, using single-cell genome technology.

Rickettsiales -like organisms are important for the survival and functioning of corals, prompting an investigation of their complete genomes. Earlier reports of the genomes of these organisms remain incomplete. Here, we report a novel draft genome of Rickettsiales bacterial strain SESOKO1, found in Acropora tenuis coral, using single-cell genome technology.

The tumor microenvironment is deeply involved in the process of tumor growth and development. In this study, we focused on cancer-associated fibroblasts (CAFs) and their derived exosomes on the lymphoma microenvironment to uncover their clinical significance. CAFs were established from primary lymphoma samples, and exosomes secreted from CAFs were obtained by standard procedures. We then investigated the roles of CAFs and their derived exosomes in the survival and drug resistance of lymphoma cells. CAFs supported the survival of lymphoma cells through increased glycolysis, and the extent differed among CAFs. Exosomes were identified as a major component of the extracellular vesicles from CAFs, and they also supported the survival of lymphoma cells. The suppression of RAB27B, which is involved in the secretion of exosomes, using a specific siRNA resulted in reduced exosome secretion and decreased survival of lymphoma cells. Moreover, anti-pyrimidine drug resistance was induced in the presence of exosomes through the suppression of the pyrimidine transporter, equilibrative nucleoside transporter 2 (ENT2), and the suppression of ENT2 was significant in in vivo experiments and clinical samples. RNA sequencing analysis of miRNAs in exosomes identified miR-4717-5p as one of the most abundant miRNAs in the exosome, which suppressed the expression of ENT2 and induced anti-pyrimidine drug resistance in vitro. Our results suggest that exosomes including miR-4717-5p secreted from CAFs play a pivotal role in the lymphoma microenvironment, indicating that they are a promising therapeutic target.

[Objective] It seems that in Japan’s aging society, investigating the position of acupuncture and moxibustion for the treatment of arteriosclerotic diseases is important. In this report we evaluated the effects of electroacupuncture (EA) on stroke patients by measuring changes in pulse wave velocity (PWV), brachial-ankle PWV (baPWV), ankle brachial pressure index (ABI), blood pressure (BP) and heart rate (HR). [Method] The subjects were 210 initial stroke patients. Stroke patients were randomly allocated to three groups, those only taking drug therapy (drug group), those taking drug therapy combined with rehabilitation (rehab group), and those taking drug therapy and rehabilitation combined with EA (EA group). 81 cerebral thrombosis patients (drug group n = 25, rehab group n = 28, EA group n = 28), 68 cerebral embolus patients (drug group n = 24, rehab group n = 20, EA group n = 24) and 61 cerebral hemorrhage patients (drug group n = 20, rehab group n = 21, EA group n = 20) were examined. For the evaluation method blood pressure pulse wave measuring equipment was used to measure PWV, baPWV, ABI, BP, and HR after two months, four months, and six months from the onset of treatment. [Results] After two months and four months there was no significant difference in blood vessel elasticity of the three cerebral thrombosis groups. Whereas after six months, compared to the drug group, the baPWV in cerebral thrombosis patients significantly decreased for the rehab group (P < 0.05) and EA group (P < 0.01). There were no significant differences in ABI, BP, or HR. Cerebral hemorrhage and cerebral embolism patients showed no significant difference in baPWV, ABI, BP, and HR. [Conclusion] We examined the effects of adding EA to the treatment of patients who suffered cerebral thrombosis, cerebral embolism, or cerebral hemorrhage. These results show that adding EA to drug treatment and rehabilitation significantly improves blood vessel elasticity and suggests that using EA would reduce the risk of cerebral thrombosis and its reoccurrence.

【目的】刺激部位の異なる鍼刺激が血管弾性に及ぼす影響について、 健常者を対象に脈波伝播速度 (Pulse Wave Velocity：PWV) を用いて検討した。 【方法】健常者70 名を対象とし、 無作為に15分間の安静を行う無刺激群 (n=10) と手三里穴 (n=23)、 足三里穴 (n=18) 、 中カン穴 (n=19) のいずれかに15分間の置鍼を行う鍼刺激群に割付けた。 血管の弾性を反映する血管弾性値 (brachial-ankle PWV score：baPWVs)、 狭窄度を反映する足首上腕血圧比 (Ankle Brachial pressure Index：ABI)、 収縮期血圧 (Systolic Blood Pressure ：SBP)、 拡張期血圧 (Diastolic Blood Pressure：DBP)、 心拍数 (Heart Rate：HR) を計測し、 刺激前後および無刺激群と各鍼刺激群の群間比較を行った。 【結果】(1) 手三里穴群においてbaPWVsは、 刺激前1222±203 cm/s、 刺激後986±143 cm/s mean±S.D.と有意な低下を認め (p