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Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9
Abstract
Leukaemias and other cancers possess a rare population of cells capable of the limitless self-renewal necessary for cancer initiation and maintenance. Eradication of these cancer stem cells is probably a critical part of any successful anti-cancer therapy, and may explain why conventional cancer therapies are often effective in reducing tumour burden, but are only rarely curative. Given that both normal and cancer stem cells are capable of self-renewal, the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. However, it remains unclear whether cancer stem cells must be phenotypically similar to normal tissue stem cells or whether they can retain the identity of committed progenitors. Here we show that leukaemia stem cells (LSC) can maintain the global identity of the progenitor from which they arose while activating a limited stem-cell- or self-renewal-associated programme. We isolated LSC from leukaemias initiated in committed granulocyte macrophage progenitors through introduction of the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23). The LSC were capable of transferring leukaemia to secondary recipient mice when only four cells were transferred, and possessed an immunophenotype and global gene expression profile very similar to that of normal granulocyte macrophage progenitors. However, a subset of genes highly expressed in normal haematopoietic stem cells was re-activated in LSC. LSC ca…
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“PU.1 halpoinsufficiency causes subtle changes in hematopoietic differentiation, but is not sufficient to induce leukemia3, 9, 11, 13, 14.”
From Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia (2015) · cites this paper as [11]
In the citing paper
“Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice”
From Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia (2015) · cites this paper as [11]
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Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype
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“An example in point is that committed myeloid progenitor cells have been shown to acquire leukemia stem cells properties without changing their overall identity, and behave like stem cells through re-activation of genes normally expressed in normal primitive hematopoietic stem cells [85].”
BackgroundExploring the Origins of the Normal Prostate and Prostate Cancer Stem Cell
Kasper, S. (2008) · Stem Cell Reviews and Reports · doi:10.1007/s12015-008-9033-1 · Cited by 108
“AML can develop when expression of the fusion protein MLL-AF9 reactivates a portion of the self-renewal associated program normally expressed in hematopoietic stem cells [64].”
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“Prmt9 KD decreased LSC frequency, as shown in an in vitro limiting dilution assay 26–28 , in all three models (Extended Data Fig.”
Self-citationMEIS1 regulates an HLF-oxidative stress axis in MLL-fusion gene leukemia.
Roychoudhury, J., Clark, J., Gracia-Maldonado, G., Unnisa, Z., Wunderlich, M., Link, K. A., Dasgupta, N., Aronow, B., Huang, G., Mulloy, J., et al. (2015) · Blood · doi:10.1182/blood-2014-09-599258 · Cited by 37
Molecular mechanisms of MLL-associated leukemia
Yokoyama, A. (2015) · International journal of hematology · doi:10.1007/s12185-015-1774-4 · Cited by 37
“Mll-deficient embryos produce a smaller population of hematopoietic stem cells (HSCs), MPPs, common myeloid progenitors (CMPs) and granulocyte–macrophage progenitors (GMPs) in the fetal liver than in the control [29].”
BackgroundInfluentialIdentification of E74-like factor 1 (ELF1) as a transcriptional regulator of the Hox cofactor MEIS1
Xiang, P., Lo, C., Argiropoulos, B., Lai, C. B., ROUHI, A. M., Imren, S., Jiang, X., Mager, D. L., & Humphries, R. K. (2010) · Experimental Hematology · doi:10.1016/j.exphem.2010.06.006 · Cited by 27
“ELF1 is highly expressed in mouse hematopoietic stem cells and slightly decreased as the cells differentiate into lineage-committed cells [33].”
BackgroundLukaszewicz, A. I., McMillan, M., & Kahn, M. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901361d · Cited by 37
Transforming human blood stem and progenitor cells
Mulloy, J., Wunderlich, M., Zheng, Y., & Wei, J. (2008) · Cell Cycle · doi:10.4161/cc.7.21.6951 · Cited by 37
Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern
Dozzo, A., Galvin, A., Shin, J., Scalia, S., O’Driscoll, C. M., & Ryan, K. B. (2022) · Drug Delivery and Translational Research · doi:10.1007/s13346-022-01189-4 · Cited by 40
“AML developed within 80 days of injection into sublethal irradiated syngeneic recipients [231].”
BackgroundTIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis
Niederkorn, M., Hueneman, K. M., Choi, K., Varney, M., Romano, L. M., Pujato, M., Greis, K., Inoue, J., Meetei, R. A., & Starczynowski, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.093 · Cited by 36
“To generate a TIFAB-deficient MLL-AF9 model, Tifab−/− Lineage negative cells were transduced with retrovirus encoding MLL-AF9 and a GFP reporter (Krivtsov et al., 2006).”
Jiang, Y., Hu, T., Wang, T., Shi, X. E., Kitano, A., Eagle, K., Hoegenauer, K. A., Konopleva, M. Y., Lin, C. Y., Young, N. L., et al. (2019) · Blood · doi:10.1182/blood.2019001076 · Cited by 47
Vakkilainen, S., Skoog, T., Einarsdottir, E., Middleton, A., Pekkinen, M., Öhman, T. J., Katayama, S., Krjutškov, K., Kovanen, P., Varjosalo, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50334-6 · Cited by 36
“A Cell cycle Chromosome organization Cell cycle process Mitotic cell cycle Cellular response to stress Mitotic cell cycle process DNA metabolic process Organelle fission Nuclear division Cellular response to DNA damage stimulus Mitotic nuclear division Cell division Mitotic cell cycle phase transition Cell cycle phase…”
InfluentialEMP2 is a novel therapeutic target for endometrial cancer stem cells
Kiyohara, M., Dillard, C. M., Tsui, J. L., Kim, S. R., Lu, J., Sachdev, D., Goodglick, L., Tong, M., Torous, V. F., Aryasomayajula, C., et al. (2017) · Oncogene · doi:10.1038/onc.2017.142 · Cited by 38
ACER3 supports development of acute myeloid leukemia.
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Self-citationRNAi-mediated silencing of MLL-AF9 reveals leukemia-associated downstream targets and processes
Fleischmann, K., Pagel, P., Schmid, I., & Roscher, A. A. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-27 · Cited by 37
“Some previous studies have analyzed targets of MLL-AF9 in in vivo mouse models [3,12,13] or through lentiviral MLL-AF9 transduction [14].”
MethodMinimizing the risk of cancer: tissue architecture and cellular replication limits
Rodriguez-Brenes, I. A., Wodarz, D., & Komarova, N. L. (2013) · Journal of The Royal Society Interface · doi:10.1098/rsif.2013.0410 · Cited by 36
“Recently progenitor cell populations have been identified as targets for tumor initiation in a number of leukemias [40, 41, 42, 43, 44, 45] and several types of solid cancer, including glioblastoma, medulloblastoma, prostate cancer, basal cell carcinoma and basal-like breast cancer [46, 47, 48, 49, 50].”
BackgroundSTAT5 Is Crucial to Maintain Leukemic Stem Cells in Acute Myelogenous Leukemias Induced by MOZ-TIF2
Tam, W. F., Hähnel, P. S., Schüler, A., Lee, B. H., Okabe, R., Zhu, N., Pante, S. V., Raffel, G., Mercher, T., Wernig, G., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0255 · Cited by 36
“However, the expression of MLL-AF9 itself is able to induce a strong leukemia self-renewal and maintenance program (36, 37), whereas mice transplanted with MOZ-TIF2–transduced hematopoietic progenitors developed monoclonal or oligoclonal AML with long disease latencies indicating that a second cooperative event is req…”
BackgroundSelf-citationMolecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model
Reckzeh, K., Bereshchenko, O., Mead, A. J., Rehn, M., Kharazi, S., Jacobsen, S. E. W., Nerlov, C., & Cammenga, J. (2012) · Leukemia · doi:10.1038/leu.2012.37 · Cited by 32
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Grist for the MLL: how do MLL oncogenic fusion proteins generate leukemia stem cells?
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“When coupled with the observation that Hoxa genes are expressed at high level in murine HSCs and downregulated with terminal differentiation, it has been argued that MLL leukemias exhibit inappropriate sustained activation of key components of the transcriptional program of the HSC [ 9 ].”
BackgroundInfluentialGood cells gone bad: the cellular origins of cancer
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Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML
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“(e) Abundance of the LSC enriched Lin- Sca1- c-Kit+ CD34+ CD16/CD32hi (LSCe) population among leukemic (Venus+) cells (LCs) in BM. (f) Cell cycle distribution of LSCe.”
BackgroundMethodInfluentialInhibition of mTOR kinase as a therapeutic target for acute myeloid leukemia
Tabe, Y., Tafuri, A., Sekihara, K., Yang, H., & Konopleva, M. Y. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1333600 · Cited by 44
“poietic stem cells (HSCs) or from myeloid progenitors that have acquired stemness properties, allowing the expansion of a clonal population characterized by the leukemia selfrenewal-associated signature [4].”
BackgroundTranscriptional activation by MLL fusion proteins in leukemogenesis.
Yokoyama, A. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2016.10.014 · Cited by 35
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“One-sample (A, C, and G) a xenografts indicated that LSCs are important for the onset and progression of the disease (Bonnet and Dick, 1997; Krivtsov et al., 2006; Somervaille and Cleary, 2006).”
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The role of microRNAs in hematopoietic stem cell and leukemic stem cell function
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“Mouse models of chronic myeloid leukemia (CML) and AML have provided evidence that the LSCs may arise from either population, with the specific population involved likely depending on the exact oncogenic event and disease context [Krivtsov et al. 2006; Passegue and Weisman, 2005; Cozzio et al. 2003].”
BackgroundBiphasic MLL takes helm at cell cycle control: Implications in human mixed lineage leukemia
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Stem cell‐based therapy in gastroenterology and hepatology
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“MLL-AF9–expressing retroviruses were produced in 293T cells with an MSCV-MLL-AF9-IRES-YFP encoding plasmid ( 32 ).”
MethodNon‐genetic heterogeneity, altered cell fate and differentiation therapy
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SUV39H1 regulates the progression of MLL-AF9-induced acute myeloid leukemia
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Activation of CpG-Rich Promoters Mediated by MLL Drives MOZ-Rearranged Leukemia.
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Targeting DNA binding proteins for cancer therapy
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“Interestingly, in MLL-AF9-mediated transformation of progenitor cells, TCF4 has been shown to be up-regulated.(15) In the first cohort, patients with high TCF4 expression are significantly more classified in the M0 or M1 FAB-subgroups than TCF4 patients, suggesting that the leukemic cells of the TCF4 patients derive f…”
BackgroundShen, L., Zhang, X.-F., Hu, D.-X., Feng, T., Li, H.-L., Lu, Y., & Huang, J. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1769-5 · Cited by 34
“So, cancer stem cells could originate from normal stem cells or progenitor cells after acquisition of multiple mutations [17].”
MacLean, A. L., Celso, C. L., & Stumpf, M. (2013) · Journal of the Royal Society Interface · doi:10.1098/rsif.2012.0968 · Cited by 34
Squelching Glioblastoma Stem Cells by Targeting REST for Proteasomal Degradation
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unc-3-dependent repression of specific motor neuron fates in Caenorhabditis elegans
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“Gfi-1 is expressed in HSCs and controls their proliferation, then is partially repressed as the HSCs generate committed progenitors including common lymphoid progenitors, in which O/E-1 expression is first detected (Akashi et al., 2003; Dias et al., 2005; Hock et al., 2003; Krivtsov et al., 2006).”
BackgroundStem cells, a two-edged sword: risks and potentials of regenerative medicine.
Piscaglia, A. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4273 · Cited by 34
Metastasis of Colorectal Cancer
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Role of the calcium toolkit in cancer stem cells
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Stabilization of NF-κB-Inducing Kinase Suppresses MLL-AF9-Induced Acute Myeloid Leukemia
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“The LSC immunophenotype in thismodel is well defined as lin c-kit+Sca1 CD16+CD34+ leukemia cells (Krivtsov et al., 2006).”
InfluentialEl-Badawy, A., Ghoneim, M. A., Gabr, M. M., Salah, R. A., Mohamed, I. K., Amer, M., & El‐Badri, N. (2017) · Stem Cell Research & Therapy · doi:10.1186/s13287-017-0709-9 · Cited by 34
“In addition, committed progenitors can acquire self-renewal ability and function as CSCs [14, 15].”
BackgroundMetastatic dormancy: a complex network between cancer stem cells and their microenvironment.
Bleau, A., Agliano, A., Larzábal, L., de Aberasturi, A. L., & Calvo, A. (2014) · Histology and Histopathology · doi:10.14670/hh-29.1499 · Cited by 33
“Conversely, accumulation of mutations in differentiated cells can also give rise to stem-like properties (Krivtsov et al., 2006, Jordan, 2009; Scheel et al., 2011).”
BackgroundCorepressor Rcor1 is essential for murine erythropoiesis
Yao, H., Goldman, D. C., Nechiporuk, T., Kawane, S., McWeeney, S. K., Tyner, J. W., Fan, G., Kerenyi, M. A., Orkin, S. H., Fleming, W., et al. (2014) · Blood · doi:10.1182/blood-2013-11-538678 · Cited by 32
“map: genes are ranked according to their relative expression levels in HSCs relative to CMPs, GMPs, and MEPs.(21) Colors and NES as described in (D).”
BackgroundMethodPbx1 restrains myeloid maturation while preserving lymphoid potential in hematopoietic progenitors
Ficara, F., Crisafulli, L., Lin, C., Iwasaki, M., Smith, K. S., Zammataro, L., & Cleary, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.125435 · Cited by 33
“However, it is increasingly evident that lineage-restricted progenitors can serve as targets for oncogenic mutations that induce unlimited self-renewal and confer leukemia stem cell potential (Cano et al., 2008; Cleary, 2009; Krivtsov et al., 2006; Minami et al., 2008; Signer et al., 2010; Somervaille et al., 2009; Tr…”
BackgroundGenome-Wide Analysis of Transcriptional Reprogramming in Mouse Models of Acute Myeloid Leukaemia
Bonadies, N., Foster, S. D., Chan, W.-I., Kvinlaug, B. T., Spensberger, D., Dawson, M. A., Spooncer, E., Whetton, A. D., Bannister, A. J., Huntly, B. J. P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016330 · Cited by 30
“Mixed Lineage Leukaemia (MLL) and Monocytic Leukaemia Zinc Finger (MOZ) fusion proteins have both been shown to subvert HSPCs into AML leukaemia cells in retroviral transplant mouse models [6,7,8].”
Scaffidi, P., & Misteli, T. (2010) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2010.75.007 · Cited by 33
Transformation from Committed Progenitor to Leukemia Stem Cells
Krivtsov, A. V., Feng, Z., & Armstrong, S. A. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04966.x · Cited by 23
Self-citationCell lineage and cell death: Caenorhabditis elegans and cancer research
Potts, M. B., & Cameron, S. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2984 · Cited by 30
Chen, D.-W., Fan, J., Schrey, J. M., Mitchell, D. V., Jung, S. K., Hurwitz, S. N., Pérez, E. B., Muraro, M. J., Carroll, M. P., Taylor, D. M., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02136-7 · Cited by 37
“Evaluation of the CFU colony counts con fi rmed reduced clonogenicity after exposure to C1498-EV AML compared to control (Fig.”
The molecular functions of common and atypical MLL fusion protein complexes.
Takahashi, S., & Yokoyama, A. (2020) · Biochimica et Biophysica Acta. Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2020.194548 · Cited by 32
PRDM16s transforms megakaryocyte-erythroid progenitors into myeloid leukemia–initiating cells
Hu, T., Morita, K., Hill, M. C., Jiang, Y., Kitano, A., Saito, Y., Wang, F., Mao, X., Hoegenauer, K. A., Morishita, K., et al. (2019) · Blood · doi:10.1182/blood.2018888255 · Cited by 32
Six1 regulates leukemia stem cell maintenance in acute myeloid leukemia
Chu, Y., Chen, Y., Li, M., Shi, D., Wang, B., Lian, Y., Cheng, X., Wang, X., Xu, M., Cheng, T., et al. (2019) · Cancer Science · doi:10.1111/cas.14033 · Cited by 27
“1 Heterogeneity of AML is manifested by multiple oncogenic proteins, including mixed-lineage leukemia (MLL) fusions/t(v;11q23), PML-RARα/t(15;17), AML1-ETO/t(8;21) and CBFB-MYH11/ (inv16).”
BackgroundThe Cancer Mutation D83V Induces an α-Helix to β-Strand Conformation Switch in MEF2B
Lei, X., Kou, Y., Fu, Y., Rajashekar, N., Shi, H., Wu, F., Xu, J., Luo, Y., & Chen, L. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.02.012 · Cited by 35
The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis
Liu, L., Wan, X., Zhou, P., Zhou, X., Zhang, W., Hui, X., Yuan, X., Ding, X., Zhu, R., Meng, G., et al. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0567-7 · Cited by 35
High-throughput screening in niche-based assay identifies compounds to target preleukemic stem cells
Gerby, B., Veiga, D. F. T., Krošl, J., Nourreddine, S., Ouellette, J., Haman, A., Lavoie, G., Fares, I., Tremblay, M. R., Litalien, V., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86489 · Cited by 37
Park, S.-J., Kim, J.-G., Kim, N., Yang, K., Shim, J., & Heo, K. (2016) · Oncology Letters · doi:10.3892/ol.2016.4115 · Cited by 32
Acute myeloid leukemia requires Hhex to enable PRC2-mediated epigenetic repression of Cdkn2aPreprint
Shields, B. J., Jackson, J. T., Metcalf, D., Shi, W., Huang, Q., Garnham, A. L., Glaser, S. P., Beck, D., Pimanda, J. E., Bogue, C. W., et al. (2016) · Genes & Development · doi:10.1101/gad.268425.115 · Cited by 33
“Together, these results indicate that Hhex acts independently of HoxA/Meis1 genes, which are established drivers of MLL fusion leukemia in this setting (Krivtsov et al. 2006).”
BackgroundInfluentialADCY7 supports development of acute myeloid leukemia
Li, C., Xie, J.-J., Lu, Z.-G., Chen, C., Yin, Y., Zhan, R., Fang, Y., Hu, X.-M., & Zhang, C. C. (2015) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2015.07.123 · Cited by 32
“Because MLL-AF9 transformed GMPs are enriched for AML stem cells [30], this result suggests that ADCY7 is highly expressed by leukemia stem cells.”
BackgroundWeiss, C. N., & Ito, K. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16036183 · Cited by 33
“Retroviral expression of MLL1-AF9 (ALL1-fused gene from chromosome 9, or MLLT3) in several hematopoietic compartments results in the generation of acute myeloid leukemia (AML) upon transplantation in mice, and has been used as a model to study AML and leukemia stem cells (LSCs, also known as leukemia-initiating cells)…”
MethodTheocharides, A. P. A., Dobson, S. M., Laurenti, E., Notta, F., Voisin, V., Cheng, P.-Y., Yuan, J. S., Guidos, C. J., Minden, M. D., Mullighan, C. G., et al. (2014) · Leukemia · doi:10.1038/leu.2014.150 · Cited by 25
C/EBPα: critical at the origin of leukemic transformation
Roe, J.-S., & Vakoc, C. R. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20132530 · Cited by 32
A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells
Liu, J., Mercher, T., Scholl, C., Brumme, K. M., Gilliland, D. G., & Zhu, N. (2012) · Experimental Hematology · doi:10.1016/j.exphem.2012.01.017 · Cited by 28
Self-citationNumata, M., Haginoya, N., Shiroishi, M., Hirata, T., Sato‐Otsubo, A., Yoshikawa, K., Takata, Y., Nagase, R., Kashimoto, Y., Suzuki, M., et al. (2023) · Cancer Cell International · doi:10.1186/s12935-023-02877-y · Cited by 33
“FCM analysis of murine MA9 cells treated with DMSO, DS-1594a·succinate, or Ara-C for 7 days was performed with antibodies against the LIC-associated marker c-KIT [12, 36], the granulocytic and myeloid differentiation markers CD11b and Ly-6G, and the apoptosis marker Annexin V (Fig.”
MethodHSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia
Dong, Q.-Z., Xiu, Y., Wang, Y., Hodgson, C., Borcherding, N., Jordan, C., Buchanan, J. L., Taylor, E., Wagner, B., Leidinger, M. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33861-1 · Cited by 31
Self-citationThe Subventricular Zone in Glioblastoma: Genesis, Maintenance, and Modeling
Beiriger, J., Habib, A., Jovanovich, N., Kodavali, C. V., Edwards, L., Amankulor, N., & Zinn, P. O. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.790976 · Cited by 38
“This manipulation in astrocytes results in their acquisition of stem cell-like characteristics, offering one possible explanation for the similarities between GICs and stem cells (48, 49).”
ResultDeciphering the Therapeutic Resistance in Acute Myeloid Leukemia
Gurnari, C., Pagliuca, S., & Visconte, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228505 · Cited by 31
Molecular pathogenesis of disease progression in MLL-rearranged AML
Kotani, S., Yoda, A., Kon, A., Kataoka, K., Ochi, Y., Shiozawa, Y., Hirsch, C. M., Takeda, J., Ueno, H., Yoshizato, T., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0253-3 · Cited by 34
Zhang, F., Liu, X.-Y., Chen, C.-Q., Zhu, J., Yu, Z., Xie, J.-J., Xie, L., Bai, H.-T., Zhang, Y., Fang, X., et al. (2017) · Haematologica · doi:10.3324/haematol.2016.151555 · Cited by 31
“MLL-AF9-expressing retroviruses were produced in 293T cells with an MSCV-MLL-AF9-IRES-YFP encoding plasmid.(16) Lin fetal”
MethodMEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
Wang, W., Org, T., Montel‐Hagen, A., Pioli, P. D., Duan, D., Israely, E., Malkin, D. J., Su, T., Flach, J., Kurdistani, S. K., et al. (2016) · Nature Communications · doi:10.1038/ncomms12376 · Cited by 30
“Mef2c is abnormally induced in leukaemic GMPs in myeloid leukaemia and knockdown of Mef2c attenuated the proliferative potential of these cells 50 .”
Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death
Feng, Q., Leong, W., Liu, L., & Chan, W.-I. (2016) · Molecules · doi:10.3390/molecules21040534 · Cited by 35
“Evidence has demonstrated that genetic lesions occur in the hematopoietic stem or progenitor cells, resulting in differentiation block due to acquisition of abnormal self-renewal program [1,2].”
BackgroundSomatic mutations and the hierarchy of hematopoiesis
Traulsen, A., Pacheco, J. M., Luzzatto, L., & Dingli, D. (2010) · BioEssays · doi:10.1002/bies.201000025 · Cited by 26
“CFU-GM) acquires stem cell line properties due to the acquisition of specific mutations [51–53].”
BackgroundAgrelo, R., & Wutz, A. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.09.017 · Cited by 31
Horton, S., Walf-Vorderwülbecke, V., Chatters, S., Sebire, N., de Boer, J., & Williams, O. (2008) · Blood · doi:10.1182/blood-2008-07-170480 · Cited by 31
Cancer: Inappropriate Expression of Stem Cell Programs?
Wang, J. Y., & Armstrong, S. A. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.03.014 · Cited by 25
Self-citationNew molecular concepts and targets in acute myeloid leukemia
Buzzai, M., & Licht, J. (2008) · Current opinion in hematology · doi:10.1097/moh.0b013e3282f3ded0 · Cited by 31
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Galán-Díez, M., Borot, F., Ali, A. M., Zhao, J., Gil-Iturbe, E., Shan, X., Luo, N., Liu, Y., Huang, X.-P., Bisikirska, B. C., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0692 · Cited by 38
Parmar, M. D., Pang, W., Hao, D., Jiang, J., Wang, L., Wang, L., & Zhou, Y. (2019) · IEEE Access · doi:10.1109/access.2019.2926579 · Cited by 33
“Nevertheless, the task of optimizing parameters of DBSCAN can be non-trivial [32].”
BackgroundKenda-Suster, N., Smrkolj, Š., & Virant-Klun, I. (2017) · Journal of Ovarian Research · doi:10.1186/s13048-017-0306-7 · Cited by 30
“On the other hand, it was shown on experimental cancer models that CSCs are not necessarily derived from normal stem cells [31].”
BackgroundNRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Sachs, Z., LaRue, R., Nguyen, H. T. Q., Sachs, K., Noble, K. E., Hassan, N. A. M., Diaz-Flores, E., Rathe, S., Sarver, A., Bendall, S., et al. (2014) · Blood · doi:10.1182/blood-2013-08-521708 · Cited by 30
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“…al., 2003; Ferrando et al., 2003; Forster et al., 2003; Johnson et al., 2003; Martin et al., 2003; Rozovskaia et al., 2003; Zeisig et al., 2004; Milne et al., 2005a; Milne et al., 2005b; Chen et al., 2006; Kong et al., 2006; Krivtsov et al., 2006; Meyer et al., 2006; Somervaille and Cleary, 2006).”
Stem cell identity and template DNA strand segregation
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“S7C) [20, 42] did not lead to significant differences in survival.”
BackgroundCancer Stem Cells or Tumor Survival Cells?
Teng, Y. D., Wang, L., Kabataş, S., Ulrich, H., & Zafonte, R. (2018) · Stem Cells and Development · doi:10.1089/scd.2018.0129 · Cited by 29
“SCFR Mast/stem cell growth factor receptor, CD117 Cell surface Drug resistance, cell migration and stemness [55,56]”
BackgroundPAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice
Jamrog, L. A., Chemin, G., Fregona, V., Coster, L., Pasquet, M., Oudinet, C., Rouquié, N., Prade, N., Lagarde, S., Cresson, C., et al. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1721678115 · Cited by 29
Metadata
- Authors
- Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., Golub, T. R., & Armstrong, S. A.
- Affiliations
- Boston Children's Hospital (US)
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Armstrong, Scott A.
- ORCID
- Venue
- Nature
- Published
- 2006-07-16
- Volume
- 442
- Issue
- 7104
- Pages
- 818-822
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2109336877
- Cited by
- 1,513
- References
- 0
- Citations by year
- 2026: 37 · 2025: 45 · 2024: 66 · 2023: 70 · 2022: 60 · 2021: 65 · 2020: 66 · 2019: 73 · 2018: 70 · 2017: 75 · 2016: 85 · 2015: 83 · 2014: 77 · 2013: 79 · 2012: 92
- FWCI
- 59.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- leukemia stem cells, committed progenitors, MLL-AF9 fusion, CFU-GM, self-renewal, cancer stem cells, hematopoietic stem cells, gene expression profiling, oncogenic transformation, targeted cancer therapy
- MeSH terms
- Animals, Cell Differentiation, Cell Division, Cell Line, Cell Transformation, Neoplastic, Granulocytes, Humans, Leukemia, Macrophages, Neoplasm Transplantation, Neoplastic Stem Cells, Leukemia, Myelomonocytic, Acute, Oncogene Proteins, Fusion, Survival Rate, Cell Lineage, Mice, Myeloid-Lymphoid Leukemia Protein
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