The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
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…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
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
Cited by
Sorted by citations
Items 701–800 of 1,002
The full transforming capacity of MLL-Af4 is interlinked with lymphoid lineage commitment.
Lin, S., Luo, R., Shrestha, M., Thirman, M., & Mulloy, J. (2017) · Blood · doi:10.1182/blood-2017-04-777185 · Cited by 29
Hu, Z.-W., Xu, J., Cheng, J.-J., McMichael, E. L., Yu, L., & Carson, W. (2016) · OncoTarget · doi:10.18632/oncotarget.13644 · Cited by 29
ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia
Weisberg, S., Smith-Raska, M., Esquilin, J., Zhang, J., Arenzana, T. L., Lau, C. M., Churchill, M., Pan, H., Klinakis, A., Dixon, J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.007 · Cited by 29
“Experimental overexpression of MLL fusion proteins such as MLL-AF9 (MA9) causes transformation of murine myeloid progenitors (Krivtsov et al., 2006; Somervaille and Cleary, 2006).”
BackgroundRole of cancer stem cells in hepatocarcinogenesis
Wang, B., & Jacob, S. (2011) · Genome Medicine · doi:10.1186/gm225 · Cited by 29
Marstrand, T. T., Borup, R., Willer, A., Borregaard, N., Sandelin, A., Porse, B. T., & Theilgaard‐Mönch, K. (2010) · Leukemia · doi:10.1038/leu.2010.95 · Cited by 26
Systems Biology of Tumor Dormancy
Enderling, H., Almog, N., & Hlatky, L. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-1445-2 · Cited by 29
Targeting the Wnt Pathway in Cancer
Goss, K. H., & Kahn, M. R. (2011) · Springer eBooks · doi:10.1007/978-1-4419-8023-6 · Cited by 23
Numata, A., Kwok, H. S., Kawasaki, A., Li, J., Zhou, Q.-L., Kerry, J., Benoukraf, T., Bararia, D., Li, F., Ballabio, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03854-0 · Cited by 28
MLL-AF9 leukemias are sensitive to PARP1 inhibitors combined with cytotoxic drugs.
Maifrede, S., Martinez, E., Nieborowska-Skorska, M., Marcantonio, D. D., Hulse, M., Le, B. V., Zhao, H.-Q., Piwocka, K., Tempera, I., Sykes, S., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017006247 · Cited by 28
Chemokines and chemokine receptors in stem cell circulation
Beider, K. (2008) · Frontiers in bioscience · doi:10.2741/3190 · Cited by 25
Aberrant GSK3β nuclear localization promotes AML growth and drug resistance
Ignatz-Hoover, J. J., Wang, V., Mackowski, N. M., Roe, A. J., Ghansah, I. K., Ueda, M., Lazarus, H. M., de Lima, M., Paietta, E., Fernandez, H., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2018016006 · Cited by 27
Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia
So, J., Lewis, A. C., Smith, L. K., Stanley, K. L., Franich, R. L., Yoannidis, D., Pijpers, L., Domínguez, P. M., Hogg, S. J., Vervoort, S. J., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202115203 · Cited by 30
“To that end, we sorted and analyzed cKithighCD11blow immature MN cells that are highly enriched in functional LSCs (Krivtsov et al, 2006) from mice treated with vehicle, AG636 for 1 day, or doxycycline for 1 or 4 days.”
BackgroundMethodCancer Cell-Derived Exosomes Promote HCC Tumorigenesis Through Hedgehog Pathway
Li, L., Zhao, J., Zhang, Q.-B., Tao, Y.-F., Shen, C.-H., Li, R.-D., Ma, Z., Li, J.-H., & Wang, Z.-X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.756205 · Cited by 27
IL2RA Promotes Aggressiveness and Stem Cell–Related Properties of Acute Myeloid Leukemia
Nguyen, C. H., Schlerka, A., Grandits, A. M., Koller, E., van der Kouwe, E., Vassiliou, G. S., Staber, P. B., Heller, G., & Wieser, R. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0531 · Cited by 31
Zhou, B., Jin, X.-H., Jin, W., Huang, X., Wu, Y.-F., Li, H.-Y., Zhu, W., Qin, X., Ye, H.-G., & Gao, S.-M. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02384-y · Cited by 27
Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells
Shima, H., Takamatsu-Ichihara, E., Shino, M., Yamagata, K., Katsumoto, T., Aikawa, Y., Fujita, S., Koseki, H., & Kitabayashi, I. (2018) · Blood · doi:10.1182/blood-2017-05-787226 · Cited by 29
Double sword role of EZH2 in leukemia
Safaei, S., Baradaran, B., Hagh, M. F., Alivand, M. R., Talebi, M., Gharibi, T., & Solali, S. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.12.059 · Cited by 29
Matte-Martone, C., Liu, J., Zhou, M., Chikina, M., Green, D., Harty, J., & Shlomchik, W. D. (2017) · Journal of Clinical Investigation · doi:10.1172/jci85736 · Cited by 27
“2-based retrovirus encoding the MLL-AF9 fusion cDNA and GFP (27) (gift of Scott Armstrong, Memorial Sloan Kettering Institute, New York, New York, USA).”
BackgroundMethodInfluentialCD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling
Fang, X., Chen, C.-Q., Xia, F., Yu, Z., Zhang, Y., Zhang, F., Gu, H., Wan, J.-B., Zhang, X.-C., Weng, W., et al. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0350-6 · Cited by 27
“Then, Lin fetal liver cells were isolated and infected with MLL-AF9 retroviruses with 4 μg/mL polybrene and centrifuged at 1500 rpm for 2 h at 37 °C as previously described [24].”
MethodNovel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer
Chávez‐González, A., Bakhshinejad, B., Pakravan, K., Guzmán, M. L., & Babashah, S. (2016) · Cellular Oncology · doi:10.1007/s13402-016-0297-1 · Cited by 26
Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia
Chen, L., Sun, Y., Wang, J.-Y., Jiang, H., & Muntean, A. G. (2016) · OncoTarget · doi:10.18632/oncotarget.8199 · Cited by 27
“Importantly, previously reported direct targets of MLL-FPs, such as Hoxa7, Hoxa9, Hoxa10, Meis1, Eya1, Six4, Mef2c and others were up-regulated uniformly in all MLL-FP leukemias compared to bone marrow (Figure 2B (cluster 5), Supplemental Figure 2C), suggesting these do not account for differences in disease latency r…”
BackgroundSelf-citationJanssens, D. H., & Lee, C.-Y. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.03.006 · Cited by 27
“In contrast, many leukemias and solid tumors have been described where the CSC pool more closely resembles a restricted progenitor type than a stem cell [71–75].”
BackgroundEmmert‐Streib, F., Tripathi, S., & Simoes, R. D. M. (2012) · Biology Direct · doi:10.1186/1745-6150-7-44 · Cited by 27
“For this reason, the understanding of gene expression profiles, which provide signatures of all the active genes and their interconnections in a cell, contain valuable information about the functioning of key pathways, as expressed by the hallmarks of cancer and, hence, enable a practical investigation of functional m…”
BackgroundDiverging fates of cells of origin in acute and chronic leukaemia
Kovačic, B., Hoelbl‐Kovacic, A., Litos, G., Alacakaptan, M., Schuster, C., Fischhuber, K., Kerenyi, M. A., Stengl, G., Moriggl, R., Sexl, V., et al. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100208 · Cited by 24
“Similar scenarios might also apply for diseases induced by MLL-AF9 (Krivtsov et al, 2006) and MLL-ENL (Cozzio et al, 2003).”
Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges
Dewi, D. L., Ishii, H., Kano, Y., Nishikawa, S., Haraguchi, N., Sakai, D., Satoh, T., Doki, Y., & Mori, M. (2011) · Journal of gastroenterology · doi:10.1007/s00535-011-0442-6 · Cited by 27
“The expression of MLL-AF9 fusion protein has facilitated the conversion of a committed granulocyte macrophage progenitor to a leukemic stem cell [ 50 ].”
BackgroundSearching for leukemia stem cells--not yet the end of the road?
Jordan, C. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.09.010 · Cited by 27
Khokhar, E. S., Borikar, S., Eudy, E., Stearns, T., Young, K., & Trowbridge, J. J. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.01.014 · Cited by 26
“, 2007), the self-renewal program (Krivtsov et al., 2006), hematopoietic progenitor cell populations (lymphoid (CLP), granulocyte-macrophage (preGM) and erythroid-megakaryocyte (preMegE, preCFU-E, MkP)) (Sanjuan-Pla et al.”
Targeting the Menin–KMT2A interaction in leukemia: Lessons learned and future directions
Perner, F., Gadrey, J. Y., Armstrong, S. A., & Kühn, M. W. M. (2025) · International Journal of Cancer · doi:10.1002/ijc.35332 · Cited by 26
“Recent work in a leukemia model system in which the KMT2A::MLLT3 oncogene was expressed fused to a degron-tag, for the first time shed light on the hierarchy of chromatin-related versus transcription-related events at KMT2A-fusion bound genes.”
Self-citationYe, S.-S., Xiong, F., He, X.-F., Yuan, Y., Li, D., Ye, D., Shi, L.-Z., Lin, Z., Zhao, M., Feng, S., et al. (2023) · Theranostics · doi:10.7150/thno.77404 · Cited by 26
“Since overexpression of miR-182 inhibited proliferation of leukemic cells but not normal HSPCs, we performed loss of function studies with a miR-182-/- (182KO) mice model [37, 38] to further explore miR-182 function during leukemogenesis using MLL-AF9-transformed AML model [4].”
InfluentialMiyamoto, R., Kanai, A., Okuda, H., Komata, Y., Takahashi, S., Matsui, H., Inaba, T., & Yokoyama, A. (2021) · eLife · doi:10.7554/elife.64148 · Cited by 26
COVID-19 concerns aggregate around platelets
Battinelli, E. (2020) · Blood · doi:10.1182/blood.2020007805 · Cited by 26
The multiple ways Wnt signaling contributes to acute leukemia pathogenesis
Soares‐Lima, S. C., Pombo‐de‐Oliveira, M. S., & Carneiro, F. R. G. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.2mr0420-707r · Cited by 30
Okeyo-Owuor, T., Li, Y.-N., Patel, R. M., Yang, W., Casey, E. B., Cluster, A. S., Porter, S. N., Bryder, D., & Magee, J. A. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000554 · Cited by 26
miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential
Meyer, S. E., Muench, D. E., Rogers, A. M., Newkold, T. J., Orr, E., O'Brien, E. J., Perentesis, J. P., Doench, J. G., Lal, A., Morris, P. J., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171312 · Cited by 30
“As previously described, MLL-AF9 AML is characterized by immunophenotypically mature CD11b+Gr1+ granulocyte/monocyte progenitor (GMP)–like cells (Fig. 3 G; Krivtsov et al., 2006; Somervaille and Cleary, 2006).”
InfluentialTBP loading by AF4 through SL1 is the major rate-limiting step in MLL fusion-dependent transcription
Okuda, H., Takahashi, S., Takaori-Kondo, A., & Yokoyama, A. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1222337 · Cited by 26
“mally expressed specifically in immature haematopoietic progenitors—such as the haematopoietic stem cells (HSCs).(38) MLL”
Nanomaterials for targeted drug delivery to cancer stem cells
Orza, A. I., Casciano, D. A., & Biris, A. S. (2014) · Drug Metabolism Reviews · doi:10.3109/03602532.2014.900566 · Cited by 29
“However, they may also form mutations in progenitor cells that regain their selfrenewal properties (Cozzio et al., 2003; Huntly et al., 2004; Jamieson et al., 2004; Krivtsov et al., 2006).”
BackgroundTsuzuki, S., & Seto, M. (2013) · Stem Cells · doi:10.1002/stem.1277 · Cited by 26
14-3-3 regulates the LNK/JAK2 pathway in mouse hematopoietic stem and progenitor cells.
Jiang, J., Balcerek, J., Rozenova, K. A., Cheng, Y., Bersenev, A., Wu, C., Song, Y., & Tong, W. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59719 · Cited by 26
“Four 14-3-3 isoforms ( β , ε , ζ , and η ) were previously found in the BM at the mRNA level (37, 38), with 14-3-3 η being undetectable at the protein level (data not shown).”
Human Acute Myelogenous Leukemia Stem Cells Revisited - There's More Than Meets the Eye
Majeti, R., & Weissman, I. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.01.007 · Cited by 26
“Additionally, a number of investigators have reported LSC activity in progenitor populations in mouse models of MLLinduced AML (Krivtsov et al., 2006).”
BackgroundStem Cells and the Origin and Propagation of Brain Tumors
Emmenegger, B. A., & Wechsler-Reya, R. (2008) · Journal of Child Neurology · doi:10.1177/0883073808321062 · Cited by 26
Therapeutic Implications of Leukemia Stem Cell Development
Stubbs, M. C., & Armstrong, S. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3090 · Cited by 25
“One such antigen, CD44, is highly expressed in normal HSC and LSC (3).”
BackgroundInfluentialSelf-citationNeuroblastoma stem cells – mechanisms of chemoresistance and histonedeacetylase inhibitors
Khalil, M. A., Hraběta, J., Cipro, Š., Stiborová, M., Vícha, A., & Eckschlager, T. (2012) · Neoplasma · doi:10.4149/neo_2012_093 · Cited by 25
“[9] KRIVTSOV AV, TWOMEY D, FENG Z, STUBBS MC,”
BackgroundZhang, P., Wang, T., Cui, G., Ye, R., Wan, W., Liu, T., Zheng, Y., & Zhong, Z. (2024) · Advanced Materials · doi:10.1002/adma.202407189 · Cited by 25
Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia
Kumar, S., Nagpal, R., Kumar, A., Ashraf, M. U., & Bae, Y. (2021) · Biomedicines · doi:10.3390/biomedicines9060690 · Cited by 29
“ALKBH5-depletion significantly inhibited MA9-mediated cell immortalization [91].”
MethodInfluentialTranscriptional networks in acute myeloid leukemia
Thoms, J. A. I., Beck, D., & Pimanda, J. E. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22794 · Cited by 33
Dual lysosomal-mitochondrial targeting by antihistamines to eradicate leukaemic cells
Cornet-Masana, J. M., Banús‐Mulet, A., Carbo, J. M. C. I., Torrente, M. Á., Guijarro, F., Cuesta‐Casanovas, L., Esteve, J., & Risueño, R. M. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.021 · Cited by 23
“only is capable of transforming human progenitor blood cells into AML, but also induces the aberrant expression of stem-cell genes that characterize leukaemic stem cells capable of initiating, maintaining and propagating the leukaemia [26].”
BackgroundChapellier, M., Peña-Martínez, P., Ramakrishnan, R., Eriksson, M., Talkhoncheh, M. S., Orsmark-Pietras, C., Lilljebjörn, H., Högberg, C., Hagström-Andersson, A. K., Fioretos, T., et al. (2019) · Haematologica · doi:10.3324/haematol.2018.192062 · Cited by 25
A non-cell-autonomous role for Pml in the maintenance of leukemia from the niche
Guarnerio, J., Mendez, L., Asada, N., Menon, A. V., Fung, J., Berry, K., Frenette, P. S., Ito, K., & Pandolfi, P. P. (2017) · Nature Communications · doi:10.1038/s41467-017-02427-x · Cited by 27
Myeloid leukemia switch as immune escape from CD19 chimeric antigen receptor (CAR) therapy
Perna, F., & Sadelain, M. (2016) · Translational Cancer Research · doi:10.21037/tcr.2016.08.15 · Cited by 25
“This program has been designated a self renewal-associated signature (15).”
BackgroundIdentification of MLL-fusion/MYC⊣miR-26⊣TET1 signaling circuit in MLL-rearranged leukemia
Huang, H., Jiang, X., Wang, J., Li, Y., Song, C., Chen, P., Li, S., Gurbuxani, S. K., Arnovitz, S., Wang, Y., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2015.12.032 · Cited by 28
Self-citationDanis, E., Yamauchi, T., Echanique, K. A., Haladyna, J. N., Kalkur, R. S., Riedel, S. S., Zhu, N., Xie, H.-F., Bernt, K., Orkin, S., et al. (2015) · Experimental Hematology · doi:10.1016/j.exphem.2015.06.005 · Cited by 25
Self-citationOvarian stem cells: From basic to clinical applications
Özakpınar, Ö. B. (2015) · World Journal of Stem Cells · doi:10.4252/wjsc.v7.i4.757 · Cited by 24
Tumoral reprogramming: Plasticity takes a walk on the wild side
Campos‐Sánchez, E., & Cobaleda, C. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.07.003 · Cited by 24
“Also, alteration of the bone marrow microenvironment by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor decreases the myeoloproliferative neoplasias induced by the BCR-ABL oncogene, but enhances the acute myeloid leukemia caused by the MLL-AF9 oncogene [144].”
BackgroundInfluentialCancer, stem cells and cancer stem cells: old ideas, new developments
Ghaffari, S. (2011) · F1000 Medicine Reports · doi:10.3410/m3-23 · Cited by 25
“However, there are a number of studies published that show that cancer stem cells can be generated by oncogenic transformation of stem cell progeny [12-14].”
BackgroundMultiple mutant clones in blood rarely coexist.
Dingli, D., Pacheco, J. M. D. S., & Traulsen, A. (2008) · Physical review. E, Statistical, nonlinear, and soft matter physics · doi:10.1103/physreve.77.021915 · Cited by 25
Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells
Bigoni-Ordóñez, G. D., Czarnowski, D., Parsons, T. M., Madlambayan, G. J., & Villa-Diaz, L. (2018) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x13666181002151330 · Cited by 25
Blood and Lymphatic Cancer: Targets and Therapy
Dingli, D., & Clinic, M. (n.d.) · doi:10.2147/blctt · Cited by 25
“22,23 The role of the cancer stem cell in disease progression, response to therapy and relapse is an area of active investigation.”
PU.1 and Junb: suppressing the formation of acute myeloid leukemia stem cells.
Somervaille, T. C. P., & Cleary, M. L. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.11.009 · Cited by 25
Kotini, A. G., Carcamo, S., Cruz‐Rodriguez, N., Olszewska, M., Wang, T., Demircioğlu, D., Chang, C.-J., Bernard, E., Chao, M. P., Majeti, R., et al. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-22-0167 · Cited by 37
“This might reflect previous evidence of an origin of the leukemia-initiating cells in MLLr AML from committed myeloid progenitors rather than HSC/MPPs (44 and associated transcriptome data, as a valuable resource for the stem cell, leukemia, and cancer communities.”
BackgroundDefining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging
Duarte, D., Amarteifio, S., Ang, H., Kong, I. Y., Ruivo, N., Pruessner, G., Hawkins, E., & Celso, C. L. (2018) · Immunology and Cell Biology · doi:10.1111/imcb.12216 · Cited by 24
“Altogether, the poor response to CXCR4 antagonism in AML is consistent with disappointing results from clinical studies and uncertainty about the group of patients that would benefit from this treatment strategy.13 While it has been proposed that stronger inhibitors than AMD3100 may improve treatment outcome,22,23 our…”
MethodInfluentialDysregulation of haematopoietic stem cell regulatory programs in acute myeloid leukaemia
Basilico, S., & Göttgens, B. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1535-3 · Cited by 30
“Of note,murine models [76, 79, 80] often fail to reproduce the biphenotypic feature observed in MLL-r leukaemia patients with co-expression of some myeloid and lymphoid genes.”
BackgroundCell intrinsic and extrinsic regulation of leukemia cell metabolism
Jiang, Y., & Nakada, D. (2016) · International Journal of Hematology · doi:10.1007/s12185-016-1958-6 · Cited by 26
A physical mechanism of cancer heterogeneity
Chen, C., & Wang, J. (2016) · Scientific Reports · doi:10.1038/srep20679 · Cited by 24
Self-citationChiu, Y.-C., Tsai, M.-H., Chou, W.-C., Liu, Y.-C., Kuo, Y. Y., Hou, H.-A., Lu, T., Lai, L.-C., Chen, Y., Tien, H., et al. (2015) · Leukemia · doi:10.1038/leu.2015.253 · Cited by 25
Mixed lineage leukemia protein in normal and leukemic stem cells
Yip, B., & So, C. (2013) · Experimental biology and medicine · doi:10.1177/1535370213480717 · Cited by 24
Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?
Chiodi, I., Belgiovine, C., Donà, F., Scovassi, A. I., & Mondello, C. (2011) · Cancers · doi:10.3390/cancers3011111 · Cited by 29
“In support of this notion, it was shown that committed hematopoietic cells could undergo neoplastic transformation, becoming able to initiate and maintain leukemias, after exogenous expression of leukemogenic fusion proteins [36,37].”
BackgroundHussenet, T., Dembélé, D., Martinet, N., Vignaud, J., & Manoir, S. D. (2010) · Cell Cycle · doi:10.4161/cc.9.2.10421 · Cited by 24
“In leukemia, the transformation of committed progenitors leads to the concomitant acquisition of an Embryonic Stem Cell-like molecular phenotype and the formation of cancer stem cells.(3,4) In Figure 4.”
BackgroundStem cells, DNA damage, ageing and cancer
Pazhanisamy, S. K. (2009) · Hematology/Oncology and Stem Cell Therapy · doi:10.1016/s1658-3876(09)50005-2 · Cited by 24
Giordano, A., Fucito, A., Romano, G., & Marino, I. (2007) · Frontiers in Bioscience · doi:10.2741/2328 · Cited by 24
“MLL-AF9 fusion protein derives from the translocation t(9;11)(p22;q23) and is found in human leukemias (44).”
BackgroundResultInfluentialA cell cycle hypothesis of cooperative oncogenesis (Review)
Delaval, B., & Birnbaum, D. (2007) · International Journal of Oncology · doi:10.3892/ijo.30.5.1051 · Cited by 23
Atkin‐Smith, G. K., Santavanond, J. P., Light, A., Rimes, J. S., Samson, A. L., Er, J. A. K., Liu, J. J., Johnson, D. N., Page, M. L., Rajasekhar, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52867-5 · Cited by 25
“We used MLL-AF9 cells (herein referred to as AML) generated from primary mTmG BM cells that constitutively express membrane targeted tdTomato enabling them to be traced in fl ow cytometry and imaging experiments concurrently with Flk1-GFP 43,60 .”
SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis
Yu, P.-C., Hou, D., Chang, B., Liu, N., Xu, C., Chen, X., Hu, C.-L., Liu, T., Wang, X., Zhang, Q., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.04.023 · Cited by 24
Self-citationFooks, K., Galicia-Vázquez, G., Gife, V., Schcolnik-Cabrera, A., Nouhi, Z., Poon, W. W. L., Luo, V. M., Rys, R., Aloyz, R., Orthwein, A., et al. (2022) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-022-02542-8 · Cited by 23
Cacic, D. L., Reikvam, H., Nordgård, O., Meyer, P., & Hervig, T. A. (2021) · Cancers · doi:10.3390/cancers13081870 · Cited by 22
The Role of cis- and trans-Acting RNA Regulatory Elements in Leukemia
Elcheva, I. A., & Spiegelman, V. S. (2020) · Cancers · doi:10.3390/cancers12123854 · Cited by 34
“Interestingly, transformed AML blasts expressed a conserved HSC program independent from differentiation-associated ncRNAs, similar to protein-coding genes [136,137].”
BackgroundThivakaran, A., Botezatu, L., Hönes, J. M., Schütte, J., Vaßen, L., Al-Matary, Y. S., Patnana, P. K., Zeller, A. C., Heuser, M., Thol, F. R., et al. (2018) · Haematologica · doi:10.3324/haematol.2017.167288 · Cited by 24
“MLL-AF9 is a fusion protein frequently occurring in a subset of AML patients,(2) and its expression in hematopoietic progenitors has been linked to the induction of AML in mice.(36) As a third AML mouse model, we thus used mice that developed AML through the induction of MLL-AF9 expression, the product of the t(9;11)(…”
MethodGarrison, B. S., Rybak, A., Beerman, I., Heesters, B., Mercier, F., Scadden, D., Bryder, D., Baron, R., & Rossi, D. J. (2017) · Blood · doi:10.1182/blood-2016-09-738591 · Cited by 23
Barabé, F., Gil, L., Celton, M., Bergeron, A., Lamontagne, V., Roques, É., Lagacé, K., Forest, A., Johnson, R. M., Pécheux, L., et al. (2016) · Leukemia · doi:10.1038/leu.2016.302 · Cited by 23
Goyama, S., Shrestha, M., Schibler, J., Rosenfeldt, L., Miller, W., O'Brien, E., Mizukawa, B., Kitamura, T., Palumbo, J., & Mulloy, J. (2016) · Oncogene · doi:10.1038/onc.2016.416 · Cited by 23
Glioma stem cells: turpis omen in nomen? (the evil in the name?)
Binda, E., Reynolds, B., & Vescovi, A. L. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12254 · Cited by 23
The beating heart of melanomas: a minor subset of cancer cells sustains tumor growth
Schmidt, P., & Abken, H. (2011) · Oncotarget · doi:10.18632/oncotarget.259 · Cited by 23
“At least for some solid cancers, mouse tumor cells accordingly showed improved engraftment when transplanted into fully compatible hosts [20-23], whereas this was not the case for murine leukemias [24-26].”
Plasticity and Maintenance of Hematopoietic Stem Cells During Development
Kanji, S., & Pompili, V. J. (2011) · Recent Patents on Biotechnology · doi:10.2174/187220811795655896 · Cited by 25
“It was found that Myc, Notch and leukaemic fusion proteins stimulate self-renewal of HSCs [80, 81].”
BackgroundRb and hematopoiesis: stem cells to anemia
Walkley, C. R., Sankaran, V. G., & Orkin, S. H. (2008) · Cell Division · doi:10.1186/1747-1028-3-13 · Cited by 18
“Mutations of Rb itself and other components of the "Rb pathway" occur universally in human cancer, where differentiation is perturbed, and cancer initiating cells are thought to reacquire the capacity to self-renew [5,6].”
Ginestier, C., Körkaya, H., Dontu, G., Birnbaum, D., Wicha, M. S., & Charafe‐Jauffret, E. (2007) · médecine/sciences · doi:10.1051/medsci/200723121133 · Cited by 50
Signaling Pathways in Leukemic Stem Cells
Gurska, L. M., Ames, K. T., & Gritsman, K. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-7342-8_1 · Cited by 33
Grandis, M. D., Bardin, F., Fauriat, C., Zemmour, C., Kaoutari, A. E., Sergé, A., Granjeaud, S., Pouyet, L., Montersino, C., Chrétien, A.-S., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1223 · Cited by 33
Kao, T.-W., Chen, H.-H., Lin, J., Wang, T.-L., & Shen, Y.-A. (2024) · Biochimica et biophysica acta. Reviews on cancer · doi:10.1016/j.bbcan.2024.189085 · Cited by 22
Targeting IGF2BP3 enhances antileukemic effects of menin-MLL inhibition in MLL-AF4 leukemia
Lin, T.-S. L., Jaiswal, A., Ritter, A. J., Reppas, J., Tran, T. M., Neeb, Z. T., Katzman, S., Thaxton, M. L., Cohen, A., Sanford, J. R., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023011132 · Cited by 22
“7,22 To characterize the combined effects of IGF2BP3 knockdown and menin-MLL inhibition on LICs in vitro, we seeded MI-503 – treated MLL-Af4 I3KO and NT cells into end point colony formation assays and performed fl ow cytometric analyses, including measurements of c-Kit expression, an LIC marker…”
MethodFBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia
Zhu, X., Wei, Y.-S., Yang, Q., Liu, H.-R., Zhi, Z., Zhu, D., Li, X., Hong, D., Yu, Y., & Chen, G. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01400-0 · Cited by 24
Aberrant Activity of Histone–Lysine N-Methyltransferase 2 (KMT2) Complexes in Oncogenesis
Poręba, E., Leśniewicz, K., & Durzyńska, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249340 · Cited by 31
“Such leukemia stem cell-specific transcription programs are achieved by the MLL-FP complexes that directly target genes such as HOXA9, HOXA10, and MEIS1 [120,121].”
BackgroundPerner, F., & Armstrong, S. A. (2020) · Cells · doi:10.3390/cells9122721 · Cited by 25
Self-citationPaediatric Strategy Forum for medicinal product development of epigenetic modifiers for children
Pearson, A. D. J., Stegmaier, K., Bourdeaut, F., Reaman, G. H., Heenen, D. L., Meyers, M. L., Armstrong, S. A., Brown, P. A., Carvalho, D. D. D., Jabado, N., et al. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.08.014 · Cited by 26
Self-citationInstallation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9
Zhang, L.-S., Kang, X., Lü, J., Zhang, Y., Wu, X., Wu, G., Zheng, J., Tuladhar, R., Shi, H., Wang, Q., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.039 · Cited by 28
“Much of our understanding of howMLL-AF9 promotes tumorigenesis is inferred fromMLL-AF9-associated gene expression changes, or the identification of genomic loci potentially subject to MLL-AF9-induced chromatin remodeling using ChIP-seq analysis [6,14,27,50,53,54].”
MethodO’Connor, C., Yalla, K. C., Salomé, M., Moka, H., Castañeda, E. G., Eyers, P., & Keeshan, K. (2018) · OncoTarget · doi:10.18632/oncotarget.24525 · Cited by 22
“A study of primary AML samples showed that LSC activity was enriched in subsets which phenotypically resembled murine LMPPs and GMPs [28].”
BackgroundInfluentialSarkaria, S. M., Decker, M., & Ding, L. (2018) · BioEssays · doi:10.1002/bies.201700190 · Cited by 22
Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin.
Man, N., Sun, X.-J., Tan, Y., Garcia-Cao, M., Liu, F., Cheng, G.-Y., Hatlen, M. A., Xu, H.-M., Shah, R., Chastain, N., et al. (2016) · Blood · doi:10.1182/blood-2015-11-677708 · Cited by 22
BERNASCONI, P. P., Farina, M., Boni, M., Dambruoso, I., & Calvello, C. (2016) · American Journal of Hematology · doi:10.1002/ajh.24312 · Cited by 22
RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity
Chin, D. W. L., Sakurai, M., Nah, G. S. S., Du, L. Z., Jacob, B., Yokomizo, T., Matsumura, T., Suda, T., Huang, G., Fu, X.-Y., et al. (2016) · Blood Cancer Journal · doi:10.1038/bcj.2015.105 · Cited by 22
Zhang, Y., Peng, L., Hu, T., Wan, Y., Ren, Y., Zhang, J., Wang, X., Zhou, Y., Yuan, W., Wang, Q., et al. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.12.003 · Cited by 19
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
