LEUKEMIA STEM CELL MARKERS

摘要

The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) comprising (1) measuring the expression level of human leukemic stem cell (LSC) marker genes in a biological sample collected from a subject for a transcription product or translation product of the gene as an analyte and (2) comparing the expression level with a reference value; an LSC-targeting therapeutic agent for AML capable of suppressing the expression of a gene selected from among LSC marker genes or a substance capable of suppressing the activity of a translation product of the gene; a method for producing a sample containing hematopoietic cells for autologous transplantation or allogeneic transplantation for AML patients, comprising obtaining an LSC-purged sample with at least 1 kind of LSC marker as an index; and a method of preventing or treating AML.

主权项

1. A test method for predicting the initial onset or a recurrence of acute myeloid leukemia, comprising
(1) a step of measuring the expression level of leukemic stem cell marker genes in a biological sample collected from a subject for a transcription product or translation product of the genes as an analyte, and (2) a step of comparing the expression levels obtained in the measuring step with a reference value;
wherein the leukemic stem cell marker genes are FCGR2A and 1-217 genes selected from the group consisting of:cell membrane- or extracellularly-localized genes consisting of ADFP, ALOX5AP, AZU1, C3AR1, CACNB4, CALCRL, CCL4, CCL5, CD33, CD36, CD3D, CD86, CD9, CD93, CD96, CD97, CFD, CHI3L1, CLEC12A, CLECL1, COCH, CST7, CXCL1, DOK2, EMR2, FCER1G, FUCA2, GPR109B, GPR160, GPR34, GPR84, HAVCR2, HBEGF, HCST, HGF, HLA-DOB, HOMER3, IFI30, IL13RA1, IL2RA, IL2RG, IL3RA, INHBA, ITGB2, LGALS1, LRG1, LY86, MAMDC2, MGAT4A, P2RY14, P2RY5, PLAUR, PPBP, PRG2, PRSS21, PTH2R, PTX3, REEP5, RNASE2, RXFP1, SLC31A2, SLC43A3, SLC6A6, SLC7A6, STX7, SUCNR1, TACSTD2, TIMP1, TM4SF1, TM9SF1, TNF, TNFRSF4, TNFSF13B, TYROBP, UTS2 and VNN1; cell cycle-related genes consisting of AURKA, C13orf34, CCNA1, DSCC1, FAM33A, HPGD, NEK6, PYHIN1, RASSF4, TXNL4B and ZWINT; apoptosis-related genes consisting of MPO, IER3, BIK, TXNDC1, GADD45B and NAIP; signaling-related genes consisting of AK5, ARHGAP18, ARRB1, DUSP6, FYB, HCK, LPXN, MS4A3, PAK11P1, PDE9A, PDK1, PRKAR1A, PRKCD, PXK, RAB20, RAB8A, RABIF, RASGRP3, RGS18 and S100A11; transcription factor genes consisting of WT1, MYC and HLX; and other genes consisting of ACTR2, ALOX5, ANXA2P2, ATL3, ATP6V1B2, ATP6V1C1, ATP6V1D, C12orf5, C17orf60, C18orf19, C1GALT1C1, C1orf135, C1orf163, C1orf186, C6orf150, CALML4, CCT5, CLC, COMMD8, COTL1, COX17, CRIP1, CSTA, CTSA, CTSC, CTSG, CYBB, CYP2E1, DENND3, DHRS3, DLAT, DLEU2, DPH3, EFHD2, ENC1, EXOSC3, FAM107B, FAM129A, FAM38B, FBX022, FLJ14213, FNDC3B, GNPDA1, GRPEL1, GTSF1, HIG2, HN1, HVCN1, IDH1, IDH3A, IKIP, KIF2C, KYNU, LCMT2, ME1, MIRN21, MKKS, MNDA, MTHFD2, MYO1B, MYO1F, NAGA, NCF2, NCF4, NDUFAF1, NP, NRIP3, OBFC2A, PARP8, PDLIM1, PDSS1, PGM2, PIGK, PIWIL4, PPCDC, PPIF, PRAME, PUS7, RPP40, RRM2, S100A16, S100A8, S100P, S100Z, SAMHD1, SH2D1A, SPCS2, SPPL2A, TESC, THEX1, TMEM30A, TMEM33, TRIP13, TUBB6, UBASH3B, UGCG, VSTM1, WDR4, WIT1, WSB2 and ZNF253; and
wherein when the expression of two or more leukemic stem cell marker genes in the subject is significantly higher than the reference value, a possible presence of a leukemic stem cell in the collected biological sample or the subject's body is suggested.