Blood&Genomics

Guideline for the collection and preparation of non-transfusion autologous platelet concentrate or platelet-rich plasma from patients in hospitals

Jianjun Wu, Guiqiu Shan, Maohong Bian, Xin Cui, Guoliang Ding, Yahan Fan, Jianping Li, Zhongjun Li, Jiubo Liu, Hua Lu, Qun Luo, Shijie Mu, Mei Qin, Haiyan Wang, Jiang Wu, Daiquan Xia, Rong Xia, Pu Xu, Guihua Yang, Wen Yin, Zebo Yu, Juan Zhang, Lili Zhu, Peiyuan Zhu, Jiwu Gong, Shuming Zhao

2021, 5(2): 73-82. doi: 10.46701/BG.2021022021128

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Abstract:
Non-transfusion autologous platelet concentrate (PC), also known as platelet-rich plasma (PRP), has become a widely used blood-based product in the field of sports medicine, rehabilitation medicine, and clinical medicine. Currently, autologous PC or PRP operation procedures (personnel qualification, equipment, methods, environment and tracking, protocols, preparations, techniques and product quality control) lack unified specifications and standards, which lead to inconsistencies in the quality of PC or PRP products made by medical institutions, affecting treatment efficiency. In blood collection and supply organizations, the collection of blood components has a series of standard operating procedures (SOP) and quality assurance which can be referenced by medical institutions to standardize the preparation and usage of patient autologous PC or PRP products. According to Technical Standards for Preparation of Platelet Concentrate for Blood Stations, we compiled this guideline for medical staff to prepare high quality and reliable PC or PRP products in order to promote the standardization of PC or PRP in clinical application.

Single cell human genomic analyses: a way to refine the knowledge of cellular heterogeneity origins in individual subject

Gradimir Misevic

2021, 5(2): 83-96. doi: 10.46701/BG.2021022021112

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Abstract:
Single cell genomics performed on individual human subjects' tumors, neural tissues, and sperm samples revealed the existence of genetic heterogeneity arising through either mutations in exomes, deletions, recombinations, and duplications of DNA sequences, as well as aneuploidy. These genetic changes happen during cell cycles followed by cell division. The aim of this review is to strictly focus on single cell human genomics and intends to deliver information that can help to refine fundamental knowledge relating to genetic causes of cellular heterogeneity origins in both healthy and disease states. Allogenic heterogeneity as well as heterogeneity origins of cells possessing the same genome with different gene expression patterns is not the subject of this review. Future research still requires: a) improvement for complete and errorless DNA acquisition and sequencing of not only selected parts of the genome, and b) analyses of more samples that contain millions of cells. These data will deliver a more precise comparative representation of genetic diversity among single cells in an individual human subject. Consequently, we will be able to better distinguish between the role of genetic, versus epigenetic, and stochastic factors in the cellular diversity of over 30 trillion cells present in a human body.

The combination of DNA methyltransferase inhibitor therapy and immunotherapy for acute myeloid leukemia

Yuxuan Wu, Zou Xiang

2021, 5(2): 97-106. doi: 10.46701/BG.2021022021132

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Abstract:
Acute myeloid leukemia (AML), the most common form of acute leukemia in adults, is characterized by abnormal proliferation and blocked maturation and differentiation of myeloid precursor cells. AML is an aggressive cancer that progresses rapidly without treatment. Therefore, effective treatment modalities should be implemented immediately after diagnosis. The mainstay of classical AML therapy has been chemotherapy, which is not suitable for relapsing or refractory patients, especially elderly patients. Among emerging novel therapeutic approaches for AML, epigenetic therapy and immunotherapy represent two exciting therapeutic developments. This review focuses on discussion of the therapeutic considerations for AML from the perspective of combination treatment, which incorporates both DNA methyltransferase inhibitor therapy, as one of the most promising epigenetic therapies, and immune checkpoint inhibitor or dendritic cell-based vaccination treatments, as examples of immunotherapy. Both challenges and rationale in the optimization of therapeutic approaches, as well as recent clinical trial developments, along this line are summarized.

The progress and perspectives of CAR-T cell therapy

Yan Peng, Zhenqing Feng

2021, 5(2): 107-111. doi: 10.46701/BG.2021022021126

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Abstract:
CAR-T cell therapy has already achieved world-renowned clinical effects in the treatment of hematological malignancies. Due to the tumor heterogeneity, immunosuppressive microenvironment, and other factors, CAR-T cell therapy has still not shown obvious clinical efficacy in clinical treatment of solid tumors. However, great progress has been made in the preparation of CAR-T cells in recent years, including T cells redirected for universal cytokine mediated killing, universal CAR -T cells, non-viral vector CAR-T cells, SynNotch technology, SUPRA CAR technology, regulated CAR-T cells, and bi-specific CAR-T cells, etc. Future research and development of CAR-T cell therapy will be focused on these following aspects: the combined application of CAR-T cells with different targets, known as "Cocktail CAR-T cells", is expected to increase efficiency toward solid tumors; based on systemic biology/synthetic biology theories, CAR-T cells are likely to be transformed to robot or intelligent system by introducing sensors, logic gates, and logic circuits. This article mainly comments on research progress and perspectives on CAR-T cell therapy in solid tumor treatment.

HLA-A, -B, -C, -DRB1 and -DQB1 alleles associated with different hematological diseases in Chinese population

Lijun Wang, Dongmei Li, Jie Wang, Yuanyuan Jing, Zhongmei Wang, Yanjun Jia

2021, 5(2): 113-120. doi: 10.46701/BG.2021022021116

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Abstract:
The purpose of this study was to explore the association between human leukocyte antigens (HLA)-A, -B, -C, -DRB1 and -DQB1 allele polymorphisms and different hematological diseases in Chinese groups. Retrospective analyses of HLA genotyping data in high-resolution for patients with acute myeloid leukemia (AML, 766 cases), chronic myeloid leukemia (CML, 330 cases), acute lymphoblastic leukemia (ALL, 605 cases), aplastic anemia (AA, 229 cases), myelodysplastic syndrome (MDS, 204 cases) were performed, and the susceptible or protective HLA alleles of the above-mentioned diseases were analyzed by Chi-square test and Fisher exact test with unrelated hematopoietic stem cell donors as control. The Results indicated that A*0201, B*4402, C*0701, DRB1*1201, DRB1*1401, and DQB1*0602 might be susceptible genes of AML, while A*1101, A*3303, B*5801, C*0302, DRB1*0301, DQB1*0201 and DQB1*0502 might be protective genes of AML. A*3303 might be a protective gene of CML, and DRB1*1401 might be a susceptible gene of CML. ALL's susceptible genes included A*0201, A*0210, B*5201, DRB1*1201, DRB1*1401 and DQB1*0602, but its protective genes included DQB1*0502. For AA, A*0201, A*0206, B*1511, DRB1*0901, DRB1*1401, DQB1*0303, DQB1*0602 might be susceptible genes, while A*3303, B*5801, C*0302, DRB1*1602 and DQB1*0502 might be protective genes. A*0201, A*0206, B*1511, DRB1*0901, DRB1*1401, DQB1*0303. A*0201, B*1558, B*4801, B*5201, DRB1*1401, DRB1*1501, and DQB1*0602 might be susceptible genes of MDS, and A*3303, B*4601, B*5801, C*0302, and DRB1*0901 might be protective genes of MDS. On the basis of HLA high-resolution genotyping for the first time, this study comprehensively analyzed HLA alleles associated with different hematological diseases in the Chinese population, which should provide clues for further study on the pathogenesis of these diseases.

TCEP-HCl can resolve the daratumumab interference

Jingya Zhao, Zhixin Liu, Dandan Yin, Shijie Mu

2021, 5(2): 121-127. doi: 10.46701/BG.2021022021124

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Abstract:
Daratumumab (DARA) is a human CD38 IgG1 monoclonal antibody that has significant therapeutic effects on multiple myeloma (MM). However, DARA may interfere with the indirect antiglobulin test (IAT) used to test for MM. At present, there are defects in the popular strategies for IAT anti-human globulin reactions caused by anti-CD38 monoclonal antibody drugs. Tris(2-carboxyethyl)phosphine hydrochloride (TCEP-HCl) is a new and effective solution to eliminate DARA's interference with the IAT. To verify its effect, the following experiments were done. After TCEP-HCl was administered to red blood cells (RBCs), the expression level of CD38 antigen on RBCs was determined by flow cytometry. Serological experiments were performed to verify the effects of TCEP-HCl on different blood groups of RBCs. The results showed that DARA could cause false-positive reaction in IAT, and the CD38 antigen on the membranes of RBCs decreased after TCEP-HCl treatment. Serological results showed that TCEP-HCl did not damage other blood group antigens on RBCs, except for Kell antigens. Indirect antiglobulin tests appeared normal after treatment with the TCEP-HCl reagent. The conclusion is that TCEP-HCl can resolve daratumumab interference in the IAT.

Plasma microRNA profiling highlights miR-1260b and miR-720 as novel diagnostic and prognostic biomarkers of esophageal squamous cell carcinoma

Fuhua Wang, Yunfeng Yang, Xiangyun Guo, Feng Li, Ruihong Yang, Xiaoyu Li, Sutang Guo, Chunyan Wang

2021, 5(2): 128-134. doi: 10.46701/BG.2021022021115

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Abstract:
This paper was designed to explore the value of miRNAs as diagnostic biomarkers that may facilitate the early detection of esophageal squamous cell carcinoma (ESCC). Plasma miRNA profiles were defined via an array-based approach using samples from ESCC patients and healthy controls (n=5 each). Differentially expressed miRNAs in these samples were validated via qPCR in ESCC patients (n=96) and healthy controls (n=51), and the relationship between ESCC patient plasma miR-1260b and miR-720 levels and clinicopathological characteristics were additionally examined. In total, 12 plasma miRNAs that were differentially expressed between ESCC patients and healthy controls were identified via miRNA. Six of these miRNAs were subsequently validated, revealing that both miR-1260b and miR-720 were significantly differentially abundant in ESCC patients and controls, with miR-1260b being significantly upregulated in ESCC patients relative to controls (2.24, 1.41 respectively, P<0.001), while the opposite was observed with respect to miR-720 (0.66, 2.27 respectively, P=0.001). The use of both miR-720 and miR-1260b as a combined diagnostic tool was highly efficacious, yielding an AUC of 0.814, a sensitivity of 86.3%, and a specificity of 73.2% as a means of detecting ESCC patients. Elevated plasma miR-1260b level was also associated with a poorer patient prognosis when compared to patients with a low plasma miRNA level (P=0.021). This study has successfully developed a plasma miRNA biomarker signature of ESCC that may offer value as a diagnostic or prognostic tool when evaluating patients with ESCC.

Epiregulin promotes growth and metastasis of gastric cancer via the ERK/JNK/p38 signaling pathway

Qiuyan Xia, Jiajia Jiang, Wei Zhao, Qi Tang, Xiaohua Li, Tengqi Wang, Yan Zhou

2021, 5(2): 135-145. doi: 10.46701/BG.2021022021125

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Abstract:
Epiregulin (EREG) is a ligand of the epidermal growth factor receptor. It belongs to the ErbB family of ligands found overexpressed in various cancers such as colon cancer and lung carcinoma and is likely to play diverse oncogenic roles in several other cancer types. However, little is known about the mechanisms of EREG in the pathogenesis of gastric cancer (GC). The present study was undertaken to investigate whether EREG influences the development and progression in GC. The results revealed that EREG was found to be overexpressed in human GC cells lines. Moreover, EREG induced cell migration, invasion, and proliferation, and inhibited apoptosis in vitro. The study also found that EREG depletion inhibited tumor growth in vivo. Our findings indicated that EREG activated the ERK/JNK/p38 signaling pathway and PI3K/Akt signaling pathways to promote GC malignant progression. Overall, this study suggests that EREG may promote GC development and progression through the ERK/JNK/p38 and PI3K/Akt signaling pathways, which may improve our understanding of the molecular mechanism of EREG in GC. Thus, EREG may be a potential target for GC treatment.

Comment on "An enzymatic pathway in the human gut microbiome that converts A to universal O type blood"^[1]

Xueying Wang, Zhongjun Li

2021, 5(2): 147-148. doi: 10.46701/BG.2021022021122

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Abstract:

Treatment of stage IIIB squamous-cell lung cancer with pembrolizumab combined with chemotherapy to achieve pCR: a case report

Fanghao Liu, Haoyu Li, Yunfeng Miao, Guoli Lv

2021, 5(2): 149-153. doi: 10.46701/BG.2021022021121

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Abstract:
Lung cancer is currently the leading cause of global cancer-related deaths and its incidence increases every year. Most squamous-cell lung cancers are in the advanced stage at diagnosis. This study reported a case of a 66-year-old man diagnosed with unresectable stage IIIB squamous-cell lung cancer (cT2aN3M0), who was treated with pembrolizumab combined with paclitaxel (albumin-bound) + nedaplatin. After four cycles, a follow-up chest computed tomography (CT) scan showed the disappearance of the original right lower lobe lung mass with cavitation-like changes, and a follow-up chest CT scan 6w later revealed a solid nodule measuring approximately 1.5 cm in diameter within the cavity. Subsequent surgical excision of the residual primary lesion was performed to achieve complete pathological remission. The patient was treated with pembrolizumab combined with paclitaxel (albumin-bound) + nedaplatin and achieved complete pathological remission with surgical excision.

2021 Vol. 5, No. 2