急性髓样白血病(AML)是美国最常见的癌症之一,每年大约23,000人死亡,根据美国癌症协会更糟糕的是,通常会抵抗化疗和其他前线癌症治疗。尽管大多数患者的生存超过五年,但治疗通常正在进行中且经济上的过度。为了开发有效的治疗方法,肿瘤学和药物靶向的研究人员需要知道为什么AML对治疗如此耐药,并确定避免这种耐药性的途径。讲话bob游戏他说:“ DNA突变是癌症发展的驱动因素,”他说,Chi Wai Eric So博士,博士,博士学位,伦敦国王学院的白血病生物学教授兼主席。“但是,这些突变必须在右边发生细胞成为癌变。识别原产细胞对于了解癌症生物学和制定更好的治疗策略很重要。在这项研究中,我们重建并确定了高度侵略性和治疗性人类白血病的起源细胞。”
图1.人类HSC和CMP,但不是LMPP或GMPS是MLL融合介导的转化的细胞靶标。(a)每周针对正常和MLL转化的细胞群体测量培养物中细胞的增殖。我,mll-enl;MA6,MLL-AF6。(b)指定细胞类型的体外培养物4至6周时的典型细胞形态。比例尺,10m。(c)定义指定组分化细胞的百分比(每个原点细胞n = 4)的NBT染色。MLLX:MLL-ENL和MLL-AF6。P = 1.25×10-19,HSC-/CMP-MLLX与LMPP-/GMP-MLLX。(d)条形图代表膜联蛋白V和指定细胞的丙糖蛋白染色后每个类别中细胞的百分比。 Data are presented as means ± SD, and statistical significance of P = 0.00319 was determined by ANOVA from N=3, n=6, F- value=14.86, df=1, for HSC-/CMP-MLLx versus LMPP-/GMP-MLLx. (E) Longterm culture initiating cell (LTC-IC) frequencies of the indicated groups at 4 weeks of in vitro culture (n = 6). (F) Typical surface marker abundance of the indicated transformed cell populations at 8 to 10 weeks in culture. (G) Venn diagram showing the overlap of significantly differentially expressed (DE) genes between HSC/CMP-MLLx and LMPP/ GMP-MLLx cells using DESeq2, ANOVA (on rlog transformed read counts) and ANOVA (on vst transformed read counts) as indicated. (H) Heatmap showing the 130 genes with consistently higher expression in LMPP/GMP-MLLx and the 45 genes with consistently higher expression in HSC/CMP-MLLx and their functional annotations according to webgestalt and Toppgene. (I) Selected stem cell–related gene sets from GSEA are shown comparing HSC-/CMP-MLLx (HC-MLLx) and LMPP-/GMP-MLLx (LG/MLLx) cells. In (A), (C), and (E), data are represented as means ± SD. In (C) and (E), statistical significance was determined by Student t test. Credit: Zeisig et al., Sci. Transl. Med. 13, eabc4822 (2021) 24 February 2021
引用: FDA-approved antidiarrhea drug can reverse resistance to chemotherapy in a mouse model of leukemia (2021, March 1) retrieved 28 June 2022 from //www.pyrotek-europe.com/news/2021-03-fda-approved-antidiarrhea-drug-反向抗性。html