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Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblasti

Frontiers of Medicine 2021年第3期15卷 347-371页

作者： Jianfeng Li Yuting Dai Liang Wu Ming Zhang Wen Ouyang Jinyan Huang Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Pôle de Recherches Sino-Français en Science du Vivant et Génomique Laboratory of Molecular PathologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

B-cell precursor acute lymphoblastic leukemia(BCP-ALL)is characterized by genetic alterations with high *** subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing *** of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes,such as DUX4 rearrangements,MEF2D rearrangements,ZNF384/ZNF362 rearrangements,NUTM1 rearrangements,BCL2/MYC and/or BCL6 rearrangements,ETV6-RUNX1-like gene expression,PAX5alt(diverse PAX5 alterations,including rearrangements,intragenic amplifications,or mutations),and hotspot mutations PAX5(***80Arg)with biallelic PAX5 alterations,IKZF1(***159Tyr),and ZEB2(***1038Arg).These molecular subtypes could be classified by gene expression patterns with RNA-seq *** molecular classification greatly improved the treatment *** therapy regimens,including target inhibitors(e.g.,imatinib),immunomodulators,monoclonal antibodies,and chimeric antigen receptor T-cell(CAR-T)therapy,are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease *** provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.

关键词： BCP-ALL subtypes translocation aneuploidy sequence mutations

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Nef mutations in Long-term Non-progressors from Former Plasma Donors Infected with HIV-1 Subtype B in China

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Biomedical and Environmental Sciences 2008年第6期21卷 485-491页

作者： SHU-HUA WANG HUI XING XIANG HE FENG-XIA ZHU ZHE-FENG MENG Yu-HUA RUAN YI-MING SHAO State Key Laboratory for Infection Diseases Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China The General Hospital of Civil Aviation Administration of China Beijing 100025 China

Objective To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may influence different stages of AIDS development based on the concept that the Nef gene of HIV infection dramatically alter the severity of viral infection and virus replication and disease progression, and that long-term non-progressors （LTNP） of HIV infection are commonly associated with either a deletion of the Nef gene or the defective Nef alleles. Methods The study subjects were divided into LTNPI（n=14）, LTNP2 （n=16） and slow progressor （SP, n=19） groups for mutational analysis of the Nef sequence. The data were obtained by using Bioedit, MEGA, Anthewin and SAS software. Results Residues in Nef TA48/49 and K151 occurred more frequently in the LTNP group while AA48/49 was more frequently observed in the SP group. Of the differences observed in the secondary structure comparison using Nef consensus sequences of these three groups, one was roughly corresponding to the Nef48/49 mutation site. Conclusion TA48/49, Kiss, and AA48/49 in the Nef gene might be associated with the different stages of HIV infection, and there may be a link between the Nef secondary structure and the progression of HIV- 1 infection.

关键词： HIV-1 Nef Long-term nonprogressors sequence mutations Secondary structure prediction

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