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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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Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Self-citationA cell initiating human acute myeloid leukaemia after transplantation into SCID mice
Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M. A., & Dick, J. E. (1994) · Nature · doi:10.1038/367645a0 · Cited by 4,783
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
Jamieson, C. H. M., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., Gotlib, J., Li, K., Manz, M. G., Keating, A., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040258 · Cited by 1,485
Flagged first, then by citations
Research works printed but not linked: 26
- Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001) · DOI · Paper page
- Warner, J. K., Wang, J. C., Hope, K. J., Jin, L. & Dick, J. E. Concepts of human leukemic development. Oncogene 23, 7164–7177 (2004) · DOI
- Al-Hajj, M. & Clarke, M. F. Self-renewal and solid tumor stem cells. Oncogene 23, 7274–7282 (2004) · DOI
- Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737 (1997) · DOI
- Singh, S. K. et al. Identification of human brain tumour initiating cells. Nature 432, 396–401 (2004) · DOI
- Huntly, B. J. et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6, 587–596 (2004) · DOI · Paper page
- Cozzio, A. et al. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 17, 3029–3035 (2003) · DOI
- So, C. W. et al. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 3, 161–171 (2003) · DOI
- Lavau, C., Szilvassy, S. J., Slany, R. & Cleary, M. L. Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J. 16, 4226–4237 (1997) · DOI
- Corral, J. et al. An MLL–AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell 85, 853–861 (1996) · DOI
- Wang, J. et al. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J. 24, 368–381 (2005) · DOI
- Drynan, L. F. et al. Mll fusions generated by Cre-loxP-mediated de novo translocations can induce lineage reassignment in tumorigenesis. EMBO J. 24, 3136–3146 (2005) · DOI
- Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C. & Melton, D. A. “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298, 597–600 (2002) · DOI
- Zeisig, B. B. et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol. Cell. Biol. 24, 617–628 (2004) · DOI
- Kumar, A. R. et al. Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood 103, 1823–1828 (2004) · DOI
- Ayton, P. M. & Cleary, M. L. Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev. 17, 2298–2307 (2003) · DOI
- Armstrong, S. A. et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nature Genet. 30, 41–47 (2002) · DOI
- So, C. W., Karsunky, H., Wong, P., Weissman, I. L. & Cleary, M. L. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood 103, 3192–3199 (2004) · DOI
- Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C. & Morrison, S. J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109–1121 (2005) · DOI · Paper page
- Ross, M. E. et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood 104, 3679–3687 (2004) · DOI
- Kolligs, F. T. et al. ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation. Cancer Cell 1, 145–155 (2002) · DOI
- Abramovich, C. & Humphries, R. K. Hox regulation of normal and leukemic hematopoietic stem cells. Curr. Opin. Hematol. 12, 210–216 (2005) · DOI
- Milne, T. A. et al. MLL associates specifically with a subset of transcriptionally active target genes. Proc. Natl Acad. Sci. USA 102, 14765–14770 (2005) · DOI
- Guenther, M. G. et al. Global and Hox-specific roles for the MLL1 methyltransferase. Proc. Natl Acad. Sci. USA 102, 8603–8608 (2005) · DOI
- Du, Y., Spence, S. E., Jenkins, N. A. & Copeland, N. G. Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis. Blood 106, 2498–2505 (2005) · DOI
- Ernst, P., Mabon, M., Davidson, A. J., Zon, L. I. & Korsmeyer, S. J. An Mll-dependent Hox programme drives hematopoietic progenitor expansion. Curr. Biol. 14, 2063–2069 (2004) · DOI
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Items 901–1,000 of 1,002
Lin, G., Fei, Y.-Y., & Zhang, Y.-M. (2021) · Immunopharmacology and immunotoxicology · doi:10.1080/08923973.2021.1963272 · Cited by 15
“AML is a markedly heterogeneous and invasive malignant tumor that forms pre-LSC clones through a series of events, such as repeated mutation and fusion of the MLL gene, that leads to an abnormal program of self-renewal and supplies a selective growth advantage relative to the original cell population, ultimately resul…”
BackgroundLeukemogenesis via aberrant self‐renewal by the MLL/AEP‐mediated transcriptional activation system
Yokoyama, A. (2021) · Cancer Science · doi:10.1111/cas.15054 · Cited by 15
Grandits, A. M., Nguyen, C. H., Schlerka, A., Hackl, H., Sill, H., Etzler, J., Heyes, E. C., Stoiber, D., Grebien, F., Heller, G., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01224-2 · Cited by 18
Genua, C. D., Norfo, R., Rodríguez-Meira, A., Wen, W. X., Drissen, R., Booth, C. A. G., Povinelli, B. J., Repapi, E., Gray, N., Carrelha, J., et al. (2019) · Haematologica · doi:10.3324/haematol.2018.205351 · Cited by 18
Loke, J. C. T., Chin, P. S., Keane, P., Pickin, A., Assi, S. A., Ptasinska, A., Imperato, M. R., Cockerill, P. N., & Bonifer, C. (2018) · Blood Advances · doi:10.1182/bloodadvances.2017012781 · Cited by 17
Du, W., Amarachintha, S. P., Wilson, A. F., & Pang, Q. (2016) · Leukemia · doi:10.1038/leu.2016.242 · Cited by 17
Zeng, H.-X., Gu, H., Chen, C.-Q., Li, M., Xia, F., Xie, L., Liu, X.-Y., Zhang, F., Tong, X., Wang, J.-B., et al. (2016) · OncoTarget · doi:10.18632/oncotarget.9520 · Cited by 15
“The MSCV-MLL-AF9-IRES-YFP-encoding plasmid [46] and the packaging plasmid pCL-ECO were used to co-transfect 293T cells using the calcium phosphate transfection method.”
MethodSelf-citationTargeting Tumor Microenvironments for Cancer Prevention and Therapy
Li, V., Reid, D., & Dong, L. (2012) · InTech eBooks · doi:10.5772/28692 · Cited by 14
“, 2007), or progenitor cells that gain the ability to self-renew through oncogenic transformation (Cozzio et al., 2003; Krivtsov et al., 2006; So et al., 2004).”
BackgroundStem Cells and Somatic Cells: Reprogramming and Plasticity
Estrov, Z. E. (2009) · Clinical Lymphoma & Myeloma · doi:10.3816/clm.2009.s.031 · Cited by 18
Cancer stem cells - from initiation to elimination, how far have we reached? (Review)
Scott (2009) · International Journal of Oncology · doi:10.3892/ijo_00000278 · Cited by 14
Cancer Stem Cell Research: Current Situation and Problems
Kobayashi, N., Navarro-Alvarez, N., Soto-Gutierrez, A., Kawamoto, H., Kondo, Y., Yamatsuji, T., Shirakawa, Y., Naomoto, Y., & Tanaka, N. (2008) · Cell Transplantation · doi:10.3727/000000008783906982 · Cited by 15
Lymphoid Progenitors as Candidate Cancer Stem Cells in AML: New Perspectives
Deshpande, A., & Buske, C. (2007) · Cell Cycle · doi:10.4161/cc.6.5.3968 · Cited by 15
Cancer stem cells in hematopoietic malignancies.
Jones, R. J., & Armstrong, S. (2008) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2007.10.012 · Cited by 15
“Can AML be directly initiated from a committed myeloid progenitor cell? Recent studies in murine models have demonstrated that leukemias can be initiated from common myeloid progenitors or granulocyte macrophage progenitors [7,8].”
BackgroundSelf-citationLearning the cellular origins across cancers using single-cell chromatin landscapes
Bairakdar, M. D., Lee, W., Giotti, B., Kumar, A., Štancl, P., Wagenblast, E., Hambardzumyan, D., Polak, P. P., Karlić, R., & Tsankov, A. M. (2025) · Nature Communications · doi:10.1038/s41467-025-63957-3 · Cited by 13
“Additionally, studies using murine leukemia models and various geneticmodi fi cationsindicate thatboth HSCs and committed myeloid progenitor cells can evolve into LSCs, which phenotypically and molecularly resemble committed myeloid progenitor cells 59,60 .”
Kühn, M. W. M., Pemmaraju, N., & Heidel, F. H. (2025) · Leukemia · doi:10.1038/s41375-025-02639-x · Cited by 14
“However, when KMT2A is disrupted or altered by chromosomal translocations [28], it leads to the formation of fusion proteins that drive the development of leukemia by hijacking normal cellular mechanisms and altering gene expression pro fi les [29].”
In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy
Bowman, R. L., Dunbar, A. J., Mishra, T., Xiao, W., Waarts, M., Maestre, I. F., Eisman, S. E., Cai, L., Mowla, S., Shah, N., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.10.009 · Cited by 14
Low doses of IFN-γ maintain self-renewal of leukemia stem cells in acute myeloid leukemia
Xie, X., Zhang, W., Zhou, X., Xu, B., Wang, H., Qiu, Y., Hu, Y., Guo, B., Ye, Z., Hu, L., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02874-5 · Cited by 17
“To determine the role of IFN-γ in LSCs and AML development, we utilized an MLL-AF9-induced leukemia model in which LSCs have been shown to arise in the granulocyte-macrophage progenitor (GMP) compartment [21] or LSK BM cells [22 – 26], and treated leukemic mice with PBS or different doses of IFN-γ .”
MethodOncogenic drivers dictate immune control of acute myeloid leukemia
Austin, R. J., Straube, J., Haldar, R., Janardhanan, Y., Bruedigam, C., Witkowski, M. T., Cooper, L. T., Porter, A., Braun, M., Souza-Fonseca-Guimarães, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37592-9 · Cited by 16
“AML from primary hematopoietic stem and progenitor cells (HSPC) were generated 111 as previously described [28-30], see supplementary methods.”
DNA methyltransferase-1 in acute myeloid leukaemia: beyond the maintenance of DNA methylation
Li, M., & Zhang, D.-H. (2022) · Annals medicus · doi:10.1080/07853890.2022.2099578 · Cited by 14
“Likewise, conditional knockout of DNMT1 damages the methylation patterns and survival of LSCs. MLL-AF9-induced AML depends on DNMT1 in transformation giving rise to leukaemia, maintenance of established leukaemia, and re-establishment of leukaemia by transplanting L-GMPs [17].”
BackgroundInfluentialInterleukin‐4 treatment reduces leukemia burden in acute myeloid leukemia
Qian, F., Arner, B. E., Kelly, K. M., Annageldiyev, C., Sharma, A., Claxton, D. F., Paulson, R. F., & Prabhu, K. S. (2022) · The FASEB Journal · doi:10.1096/fj.202200251r · Cited by 16
Drug Repurposing for Targeting Acute Leukemia With KMT2A (MLL)—Gene Rearrangements
Tsakaneli, A., & Williams, O. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.741413 · Cited by 16
Epigenetic deregulation in myeloid malignancies
Huang, H.-T., & Figueroa, M. E. (2021) · Blood · doi:10.1182/blood.2019004262 · Cited by 21
Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal
Xu, J. J., Smeets, M. F. M. A., Tan, S. Y., Wall, M., Purton, L. E., & Walkley, C. R. (2018) · Experimental Hematology · doi:10.1016/j.exphem.2018.11.001 · Cited by 15
“phenotypes in experimental leukemia models [74, 75], so the use of different Cre drivers that target distinct and/or overlapping cell populations may be important in the presentation of the phenotypes in these models.”
MethodPeng, L.-Y., Tang, Y.-T., Zhang, Y.-C., Guo, S.-Q., Peng, L.-W., Ye, L., Wang, Y.-F., & Jiang, Y. (2018) · Leukemia and Lymphoma · doi:10.1080/10428194.2017.1387906 · Cited by 14
“MLL with the fusion partner protein could transform hematopoietic cells and promote leukemia [4].”
BackgroundSelf-citationNiche TWIST1 is critical for maintaining normal hematopoiesis and impeding leukemia progression
Liu, X., Ma, Y., Li, R., Guo, D., Wang, N., Zhao, Y., Yin, J., Ren, Q., Lin, Y., & Ma, X. (2018) · Haematologica · doi:10.3324/haematol.2018.190652 · Cited by 14
Vega‐García, N., Malatesta, R., Estella, C., Pérez‐Jaume, S., Esperanza‐Cebollada, E., Torrebadell, M., Català, A., Gassiot, S., Berrueco, R., Ruiz‐Llobet, A., et al. (2018) · British Journal of Haematology · doi:10.1111/bjh.15436 · Cited by 15
Identification of drug-resistant subpopulations in canine hemangiosarcoma
Khammanivong, A., Gorden, B. H., Frantz, A., Graef, A., & Dickerson, E. B. (2014) · Veterinary and Comparative Oncology · doi:10.1111/vco.12114 · Cited by 14
Mechanisms of mixed-lineage leukemia
Muntean, A. G. (2013) · International Journal of Hematologic Oncology · doi:10.2217/ijh.13.20 · Cited by 14
Cancer Stem Cells in Metastasis Therapy
Aydemir, E., & Şahin, F. (2018) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_279 · Cited by 14
Liang, Y., Russell, I., Walworth, C., & Chen, C. (2009) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v19.i4.30 · Cited by 12
KMT2A-rearranged leukemia: from mechanism to drug development
Ernst, P., Kyei, P., & Yokoyama, A. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.105247 · Cited by 9
The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development
Sturgeon, C. M., Wagenblast, E., Izzo, F., & Papapetrou, E. P. (2024) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-24-0235 · Cited by 12
“Previous mouse modeling studies have shown that committed progenitors can be the target cells of transformation in AML, by documenting that prospectively isolated progenitors harboring oncogenes can produce transplantable leukemia (63–65).”
Fotopoulou, F., Rodriguez-Correa, E., Dussiau, C., & Milsom, M. D. (2024) · Experimental Hematology · doi:10.1016/j.exphem.2024.104698 · Cited by 17
Cellular stress and epigenetic regulation in adult stem cells
Llewellyn, J., Baratam, R., Čulig, L., & Beerman, I. (2024) · Life Science Alliance · doi:10.26508/lsa.202302083 · Cited by 15
“…shown the multipotent differentiation and self-renewal capacity of HSCs is critical for maintaining the blood and immune systems throughout an organism ’ s lifespan with a loss of this tight regulation leading to maladies such as BM failure, stem cell exhaustion, and leukemia (25, 26, 27, 28, 29).”
BackgroundTherapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery
Chan, A., Han, L., Delaney, C. D., Wang, X., Mukhaleva, E., Li, M., Yang, L., Pokharel, S. P., Mattson, N. M., Garcia, M., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk3127 · Cited by 14
Self-citationVujovic, A., de Rooij, L. P. M. H., Chahi, A. K., Chen, H. T., Yee, B. A., Loganathan, S. K., Liu, L., Chan, D. C. H., Tajik, A., Tsao, E., et al. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-22-0086 · Cited by 17
“GO annotations indicate that the screen hits are involved in diverse RNA metabolic processes/interactions and molecular pathways including nitrogen compound metabolism, tRNA processing, ribosome biogenesis, and mRNA processing, indicating dependence on a broad range of posttranscriptional…”
RNA-binding proteins of KHDRBS and IGF2BP families control the oncogenic activity of MLL-AF4
Okuda, H., Miyamoto, R., Takahashi, S., Kawamura, T., Ichikawa, J., Harada, I., Tamura, T., & Yokoyama, A. (2022) · Nature Communications · doi:10.1038/s41467-022-34558-1 · Cited by 13
Liang, B., Jiang, D., Pan, L., Xiong, F., Feng, S., Wu, S.-H., Ye, H.-G., Yu, Z.-J., Shi, C.-C., & Gao, S.-M. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.04.005 · Cited by 13
Kumar, R., Pereira, R. S., Niemann, J., Azimpour, A., Zanetti, C., Karantanou, C., Minka, W., Minciacchi, V., Kowarz, E., Meister, M., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021005992 · Cited by 13
Wang, Y., Lü, T., Sun, G., Zheng, Y., Yang, S., Zhang, H., Hao, S., Liu, Y., Ma, S., Zhang, H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13411-y · Cited by 20
Self-citationSALL1expression in acute myeloid leukemia
Salman, H., Shuai, X., Nguyen‐Lefebvre, A. T., Giri, B., Ren, M., Rauchman, M. I., Robbins, L., Hou, W., Körkaya, H., & Ma, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.23448 · Cited by 14
“These leukemia generating cells, the LSCs, can arise from the neoplastic transformation of normal HSPCs [2, 3].”
BackgroundInfluentialGenetically engineered mouse models of human B-cell precursor leukemias
Hauer, J., Borkhardt, A., Sánchez-García, I., & Cobaleda, C. (2014) · Cell Cycle · doi:10.4161/15384101.2014.949137 · Cited by 15
“Also, it has been described that retrovirally transduced MLL-AF9 can transform both early haematopoietic progenitors(78) and committed myeloid progenitors.(79) However, when studying the role of Mll-AF9 in knock-in mice, it was found that there are high expression levels of the oncogene and its downstream target genes…”
BackgroundCancer stem cells: A shifting subpopulation of cells with stemness?
Hu, Y., Yu, X., Liu, S., & Liu, S. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.01.009 · Cited by 11
“[54] In that work, the MLL-AF9 fusion protein”
Isolated Hoxa9 overexpression predisposes to the development of lymphoid but not myeloid leukemia
Beachy, S., Onozawa, M., Silverman, D. A., Chung, Y., Rivera, M., & Aplan, P. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.02.006 · Cited by 13
Oncogenesis and cancer stem cells: current opinions and future directions
Cheng, X., & O'Neill, H. C. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00664.x · Cited by 11
Melanoma stem cells: targets for successful therapy?
Houben, R., Wischhusen, J., Menaa, F., Synwoldt, P., Schrama, D., Bröcker, E., & Becker, J. C. (2008) · Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · doi:10.1111/j.1610-0387.2008.06786.x · Cited by 13
Cancer biology: A game of subversion
Passegué, E. (2006) · Nature · doi:10.1038/442754a · Cited by 13
Characterization of Arsenic-Induced Cancer Stem-Like Cells.
Chang, Q., Bi, Z.-Y., Fu, Y., Rice, M., Zhang, Q., Wadgaonkar, P., Almutairy, B., Zhang, W.-X., Lu, Y.-J., Xu, L., et al. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0301-7_19 · Cited by 13
Wang, L.-L., Chen, Y.-X., Zang, M.-T., Zhou, J.-Y., Xiao, M.-Y., Fu, H.-X., Mo, X.-D., Wang, F.-R., Han, W., Zhang, Y.-Y., et al. (2025) · Cancer · doi:10.1002/cncr.35717 · Cited by 12
“62,63 It seems important to screen for KMT2A ‐ r and EVI1 genes aberrancies not linked to active leukemia.”
Self-citationThe role of exosomes in the stemness maintenance and progression of acute myeloid leukemia
Li, Q., Wang, M., & Liu, L. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115539 · Cited by 11
Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells
Wang, C., Nistala, R., Cao, M., Pan, Y., Behrens, M., Doll, D. C., Hammer, R., Nistala, P., Chang, H., Yeh, E. T. H., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112105 · Cited by 12
“…more restricted AML stem cell (AML-SC) population in this model, GMP-like leukemic (L-GMP) cells (YFP + Lin − Sca-1 − Kit + CD34 + Fc γ RII/III + ), 17 had increased levels of DPP4 expression when compared with normal GMP cells (YFP − GMP) after MLL-AF9 transformation (Figure S2A), which is…”
BackgroundMethodInfluentialThe bone marrow niche regulates redox and energy balance in MLL::AF9 leukemia stem cells
Viñado, A. C., Calvo, I. A., Cenzano, I., Olaverri-Mendizabal, D., Cócera, M., Martín‐Úriz, P. S., Romero, J. P., Vilas‐Zornoza, A., Vera, L., Gómez-Cebrián, N., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01601-5 · Cited by 17
“Here, by using a murine model of MLL::AF9 induced AML [4], we demonstrate that early mesenchymal stromal cells (MSCs) are an integral part of the MLL::AF9 derived AML niche and control LSC maintenance.”
BackgroundMethodThe histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development
Stamos, D. B., Clubb, L. M., Mitra, A., Chopp, L. B., Nie, J., Ding, Y., Das, A., Venkataganesh, H., Lee, J., El-Khoury, D., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202012 · Cited by 12
Repurposing of Anticancer Stem Cell Drugs in Brain Tumors
Bahmad, H. F., Daher, D., Aljamal, A. A., Elajami, M. K., Oh, K. S., Moreno, J. C. A., Delgado, R. G., Suarez, R., Zaldivar, A., Azimi, R., et al. (2021) · Journal of Histochemistry & Cytochemistry · doi:10.1369/00221554211025482 · Cited by 12
Zhou, B., Qin, Y., Zhou, J., Ruan, J., Xiong, F., Dong, J., Huang, X., Yu, Z., & Gao, S. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16377 · Cited by 11
Wang, Z.-H., Zhang, Y., Zhu, S.-C., Peng, H.-L., Chen, Y., Cheng, Z., Liu, S.-F., Luo, Y.-Y., Li, R.-J., Deng, M., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02949-1 · Cited by 12
Sarrou, E., Richmond, L., Carmody, R., Gibson, B., & Keeshan, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124266 · Cited by 12
“These methods benefit from its speed and ease of use [36,37] and has led to the identification of both the HSC and the granulocyte”
BackgroundMethodMolecular mechanisms for stemness maintenance of acute myeloid leukemia stem cells
Wang, J., Wang, P., Zhang, T., Gao, Z., Wang, J., Feng, M., Yin, R. L., & Zhang, H. (2019) · Blood Science · doi:10.1097/bs9.0000000000000020 · Cited by 15
“granulocyte macrophage progenitors (GMP, IL7R Lin Sca-1 c-KitCD34FcgRII/III), calledL-GMP, can function asLSCs and initiate AML development after transplanting into syngeneic recipient mice.(11) Retrovirus-mediated transduction and transplantation model is also used for other oncogenic events in studying AML pathogene…”
BackgroundSelf-citationThe Impact of the Cellular Origin in Acute Myeloid Leukemia: Learning From Mouse Models
Fisher, J. N., Kalleda, N., Stavropoulou, V., & Schwaller, J. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000152 · Cited by 19
Hif-1α Deletion May Lead to Adverse Treatment Effect in a Mouse Model of MLL-AF9-Driven AML
Velasco-Hernández, T., Soneji, S., Hidalgo, I., Erlandsson, E., Cammenga, J., & Bryder, D. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.11.023 · Cited by 19
“The higher numbers of c-Kit cells in the Hif-1a chemotherapy group might therefore be an indicator of higher drug resistance of these cells, with c-Kit being a well-described stem cell marker of murine MLL-AF9-driven LSCs (Krivtsov et al., 2006).”
BackgroundChu, S. H., Song, E. J., Chabon, J. R., Minehart, J. C., Matovina, C. N., Makofske, J. L., Frank, E. S., Ross, K. N., Koche, R. P., Feng, Z., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2018021592 · Cited by 15
Self-citationBiliary tract cancer stem cells - translational options and challenges
Mayr, C., Ocker, M., Ritter, M., Pichler, M., Neureiter, D., & Kiesslich, T. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i14.2470 · Cited by 14
Targeting the Warburg effect for leukemia therapy: Magnitude matters
Wang, Y.-H., & Scadden, D. (2015) · Molecular & Cellular Oncology · doi:10.4161/23723556.2014.981988 · Cited by 12
“We tested two leukemia models, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), which are driven by BCR-ABL–transformed stem cells and MLL-AF9–transformed progenitor cells respectively.(7,8) In both models, deletion of Pkm2 or Ldha markedly delayed leukemia initiation.”
MethodSelf-citationKurpios, N. A., Girgis-Gabardo, A., Hallett, R., Rogers, S. Y., Gludish, D., Kockeritz, L. K., Woodgett, J., Cardiff, R., & Hassell, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058151 · Cited by 12
Myelopoiesis and Myeloid Leukaemogenesis in the Zebrafish
Forrester, A. M., Berman, J. N., & Payne, E. M. (2012) · Advances in Hematology · doi:10.1155/2012/358518 · Cited by 12
“In mice, the use of lineage-restricted myeloid promoters, for example, CathepsinG [68, 69], Mrp8 [69, 70], has not limited the success of oncogenic transformation and, in fact, committed myeloid progenitor cells have been identified as the leukaemiainitiating cell (LIC) in many karyotypes of AML [69–73].”
BackgroundCD133: A MARKER OF TRANSIT AMPLIFICATION RATHER THAN STEM CELL PHENOTYPE IN THE PROSTATE?
Grey, B., Oates, J., Brown, M. D., & Clarke, N. (2009) · BJU International · doi:10.1111/j.1464-410x.2008.08250.x · Cited by 12
Martino, V., Bianchera, A., Reia, L., Bussolati, O., Fazzina, R., Marino, F., Montemurro, L., Tonelli, R., Pession, A., Gazzola, G., et al. (2009) · Molecular Medicine Reports · doi:10.3892/mmr_00000090 · Cited by 12
Identification of progenitor cancer stem cell in lentigo maligna melanoma
Bongiorno, M. R., Doukaki, S., Malleo, F., & Aricó, M. (2008) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2008.00193.x · Cited by 12
“Finally, tumor cells may undergo genetic and/or epigenetic modifications that result in the manifestation of a plastic, pluripotent phenotype (24).”
BackgroundStochastic model of the formation of cancer metastases via cancer stem cells
Zhdanov, V. (2008) · European Biophysics Journal · doi:10.1007/s00249-008-0341-9 · Cited by 12
Mixed lineage leukemia translocations and a leukemia stem cell program.
Faber, J., & Armstrong, S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0972 · Cited by 12
Self-citationEpigenetic Mechanisms in Acute Myeloid Leukemia
Peters, A. H. F. M., & Schwaller, J. (2010) · Springer eBooks · doi:10.1007/978-3-7643-8989-5_10 · Cited by 9
Wu, M., Wang, W., Mao, X., Wu, Y., Jin, Y., Liu, T., Lu, Y., Dai, H., Zeng, S., Huang, W., et al. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116539 · Cited by 12
Self-citationDistinct and targetable role of calcium-sensing receptor in leukaemia
Pereira, R. S., Kumar, R., Cais, A., Paulini, L., Kahler, A., Bravo, J., Minciacchi, V. R., Krack, T., Kowarz, E., Zanetti, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41770-0 · Cited by 13
“8k, l), which harbour the LSC fraction in this model 23 , in the BM or spleen of mice transplanted with MLL-AF9 + wildtype or CaSR KO LIC 12 days after transplantation.”
Targeting Menin and CD47 to Address Unmet Needs in Acute Myeloid Leukemia
Matthews, A. H., Pratz, K. W., & Carroll, M. P. (2022) · Cancers · doi:10.3390/cancers14235906 · Cited by 13
“Transcription of the latter two genes promotes self-renewal through stem-cell like transcription programs [29,37,42] and is critically dependent on the KMT2A-fusion protein binding to menin [17,43].”
BackgroundQuiescence regulation by normal haematopoietic stem cells and leukaemia stem cells
Gudmundsson, K. O., & Du, Y. (2022) · FEBS Journal · doi:10.1111/febs.16472 · Cited by 10
Modulators of histone demethylase JMJD1C selectively target leukemic stem cells
Yang, Y., Zhang, X.-J., Zhang, X.-Y., Wang, Y.-S., Wang, X.-T., Hu, L., Zhao, Y., Wang, H., Wang, Z.-J., Wang, H., et al. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.13054 · Cited by 11
Self-citationMir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes
Marshall, A., Kasturiarachchi, J., Datta, P., Guo, Y.-P., Deltcheva, E., James, C., Brown, J., May, G., Anandagoda, N., Jackson, I., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-76218-8 · Cited by 11
Meningioma 1 is indispensable for mixed lineage leukemia-rearranged acute myeloid leukemia
Sharma, A., Jyotsana, N., Gabdoulline, R. R., Heckl, D., Kuchenbauer, F. C., Slany, R. K., Ganser, A., & Heuser, M. (2019) · Haematologica · doi:10.3324/haematol.2018.211201 · Cited by 14
“One important difference between MN1 and MLL-r leukemia is that MN1 cannot activate Hox gene expression by itself, while MLL-AF9 can.(23,24) Therefore, MN1 is unable to transform GMP cells, while MLL-AF9 can transform myeloid progenitor cells down to the differentiation state of a GMP.”
BackgroundmiR-101 suppresses the development of MLL-rearranged acute myeloid leukemia
Gonzales-Aloy, E., Connerty, P., Salik, B., Liu, B., Woo, A., Haber, M., Norris, M., Wang, J.-L., & Wang, J. (2019) · Haematologica · doi:10.3324/haematol.2018.209437 · Cited by 11
“Transformation by MLL fusion proteins is primarily mediated through direct upregulation of the HOXA-cluster genes and HOX co-factors such as MEIS1.”
BackgroundInfluentialSelf-citationJabbar, S., Reuhl, K., & Sarkar, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-25785-y · Cited by 11
Herzig, J., Bullinger, L., Tasdogan, A., Zimmermann, P., Schlegel, M., Teleanu, V., Weber, D., Rücker, F. G., Paschka, P., Dolnik, A., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21119 · Cited by 12
Acute myeloid leukemia stem cell function is preserved in the absence of autophagy
Porter, A. H., Mouttie, L. L.-E., Vu, T., Bruedigam, C., Sutton, J., Jacquelin, S., Hill, G., Macdonald, K., & Lane, S. (2017) · Haematologica · doi:10.3324/haematol.2017.166389 · Cited by 11
“We first aimed to document the change in autophagic flux on leukemic transformation of normal stem cell populations using a well characterized retroviral model of MLL-AF9-induced AML; this is the most common genetic mutation found in infant AML and is associated with poor prognosis.(10,11)MLL-rearranged leukemia is co…”
MethodBrethon, B., Cavé, H., Fahd, M., & Baruchel, A. (2016) · Bulletin du Cancer · doi:10.1016/j.bulcan.2015.11.009 · Cited by 11
Cancer stem cells in head and neck squamous cell carcinoma.
Szafarowski, T., & Szczepański, M. J. (2014) · Otolaryngologia polska = The Polish otolaryngology · doi:10.1016/j.otpol.2013.10.010 · Cited by 11
Kamezaki, K., Luchsinger, L. L., & Snoeck, H. (2013) · Experimental Hematology · doi:10.1016/j.exphem.2013.11.008 · Cited by 11
“BM cells immortalized by MLL-ENL and MLL-AF9 form replatable colonies (AML-CFUs) in semisolid media[21, 22, 24, 26].”
BackgroundMicroRNAs mark in the MLL-rearranged leukemia
Benetatos, L., & Vartholomatos, G. (2013) · Annals of Hematology · doi:10.1007/s00277-013-1803-4 · Cited by 11
Huang, J., Shen, L., Lu, Y., Li, H.-L., Zhang, X.-F., Hu, D.-X., Feng, T., & Song, F.-Z. (2012) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.1060 · Cited by 11
“…having similar properties, such as differentiation, self-renewal, similar surface markers and sharing tightly regulated self-renewal pathways, including the Notch (10), Wnt (11) and sonic hedgehog (Shh) pathways (12), CSCs are considered to originate from normal stem cells or progenitor cells (13).”
Prindull, G. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2008.07.009 · Cited by 9
Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention
Atkinson, S. P., & Keith, W. N. (2007) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399407000269 · Cited by 12
BCR-ABL induces opposite phenotypes in murine ES cells according to STAT3 activation levels.
Coppo, P., Dusanter-Fourt, I., Vainchenker, W., & Turhan, A. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2008.09.006 · Cited by 11
Cuevas, D., Amigo, R., Agurto, A., Heredia, A. A., Guzmán, C., Recabal-Beyer, A., Gonzalez-Pecchi, V., Caprile, T., Haigh, J. J., & Farkas, C. (2024) · Biomedicines · doi:10.3390/biomedicines12081915 · Cited by 10
Metabolic reprogramming regulated by TRAF6 contributes to the leukemia progression
Matsui, S., Ri, C., Bolanos, L. C., Choi, K., Shibamiya, A., Ishii, A., Takaishi, K., Oshima‐Hasegawa, N., Tsukamoto, S., Takeda, Y., et al. (2024) · Leukemia · doi:10.1038/s41375-024-02245-3 · Cited by 10
“To generate a Traf6 -de fi cient MLL-AF9 model, Traf6 + / + ;Mx1-Cre , Traf6 fl / fl ;Mx1-Cre , Traf6 + / + ;R26-CreERT2 and Traf6 fl / fl ;R26-CreERT2 lineage negative (Lin − ) BM cells from C57Bl/6 mice were transduced with retrovirus encoding MLL-AF9 and a GFP reporter [22].”
Precision Medicine Approaches in Acute Myeloid Leukemia with Adverse Genetics
Santoro, N., Salutari, P., Ianni, M. D., & Marra, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084259 · Cited by 10
Murphy, L. A., & Winters, A. C. (2023) · Biomedicines · doi:10.3390/biomedicines11123248 · Cited by 10
“KMT2A rearrangements activate a transcriptional program characterized by upregulation of HOXA genes and MEIS1 , which are associated with lineage-inappropriate expression of stemness markers [149,150].”
BackgroundAbemaciclib drives the therapeutic differentiation of acute myeloid leukaemia stem cells
Xie, X., Zhang, W.-J., Zhou, X., Ye, Z.-X., Wang, H., Qiu, Y.-Q., Pan, Y.-T., Hu, Y., Li, L., Chen, Z.-Z., et al. (2023) · British Journal of Haematology · doi:10.1111/bjh.18735 · Cited by 10
Dissection of the MEF2D-IRF8 transcriptional circuit dependency in acute myeloid leukemia
Pingul, B. Y., Huang, H., Chen, Q., Alikarami, F., Zhang, Z., Qi, J., Bernt, K. M., Berger, S. L., Cao, Z., & Shi, J. (2022) · iScience · doi:10.1016/j.isci.2022.105139 · Cited by 10
“The dysregulation of these TFs are commonly reliant on certain types of AML including those harboring KMT2A-r or KMT2A-amp (Figure 1C) (Cao et al., 2021; Krivtsov et al., 2006; Lu et al., 2018; Zuber et al., 2011a,2011b).”
BackgroundXu, X., Wang, J., Tong, T., Zhang, W., Wang, J., Ma, W., Wang, S., Zhou, D., Wu, J., Jiang, L., et al. (2022) · Haematologica · doi:10.3324/haematol.2021.280290 · Cited by 16
Self-citationStem Cells in the Myelodysplastic Syndromes
Zhan, D., & Park, C. Y. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.719010 · Cited by 12
Brown, M. A., Edwards, M. A., Alshiraihi, I., Geng, H., Dekker, J. D., & Tucker, H. O. (2020) · Genes and Immunity · doi:10.1038/s41435-020-0094-8 · Cited by 12
Thiopurine-mediated impairment of hematopoietic stem and leukemia cells in Nudt15R138C knock-in mice
Tatsumi, G., Kawahara, M., Imai, T., Nishishita-Asai, A., Nishida, A., Inatomi, O., Yokoyama, A., Kakuta, Y., Kito, K., & Andoh, A. (2019) · Leukemia · doi:10.1038/s41375-019-0583-9 · Cited by 10
“kemia recurrence model by applying the MLL-AF9 leukemia model [32, 33].”
BackgroundMethod
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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