The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target.
acute myeloid leukaemia
clinical targeting
critical re-evaluation
identification
leukaemic stem cells
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
pubmed:
3
8
2019
medline:
10
6
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real-time benefit for AML patients.
Types de publication
Historical Article
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-156Informations de copyright
© 2019 British Society for Haematology and John Wiley & Sons Ltd.
Références
Abarrategi, A., Foster, K., Hamilton, A., Mian, S.A., Passaro, D., Gribben, J., Mufti, G. & Bonnet, D. (2017) Versatile humanized niche model enables study of normal and malignant human hematopoiesis. Journal of Clinical Investigation, 127, 543-548.
Abelson, S., Collord, G., Ng, S.W.K., Weissbrod, O., Mendelson Cohen, N., Niemeyer, E., Barda, N., Zuzarte, P.C., Heisler, L., Sundaravadanam, Y., Luben, R., Hayat, S., Wang, T.T., Zhao, Z., Cirlan, I., Pugh, T.J., Soave, D., Ng, K., Latimer, C., Hardy, C., Raine, K., Jones, D., Hoult, D., Britten, A., McPherson, J.D., Johansson, M., Mbabaali, F., Eagles, J., Miller, J.K., Pasternack, D., Timms, L., Krzyzanowski, P., Awadalla, P., Costa, R., Segal, E., Bratman, S.V., Beer, P., Behjati, S., Martincorena, I., Wang, J.C.Y., Bowles, K.M., Quiros, J.R., Karakatsani, A., La Vecchia, C., Trichopoulou, A., Salamanca-Fernandez, E., Huerta, J.M., Barricarte, A., Travis, R.C., Tumino, R., Masala, G., Boeing, H., Panico, S., Kaaks, R., Kramer, A., Sieri, S., Riboli, E., Vineis, P., Foll, M., McKay, J., Polidoro, S., Sala, N., Khaw, K.T., Vermeulen, R., Campbell, P.J., Papaemmanuil, E., Minden, M.D., Tanay, A., Balicer, R.D., Wareham, N.J., Gerstung, M., Dick, J.E., Brennan, P., Vassiliou, G.S. & Shlush, L.I. (2018) Prediction of acute myeloid leukaemia risk in healthy individuals. Nature, 559, 400-404.
Ailles, L.E., Gerhard, B. & Hogge, D.E. (1997) Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood, 90, 2555-2564.
Aiuti, A., Webb, I.J., Bleul, C., Springer, T. & Gutierrez-Ramos, J.C. (1997) The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. Journal of Experimental Medicine, 185, 111-120.
Alexander, T.B., Lacayo, N.J., Choi, J.K., Ribeiro, R.C., Pui, C.H. & Rubnitz, J.E. (2016) Phase I study of selinexor, a selective inhibitor of nuclear export, in combination with fludarabine and cytarabine, in pediatric relapsed or refractory acute leukemia. Journal of Clinical Oncology, 34, 4094-4101.
Alkharabsheh, O. & Frankel, A.E. (2019) Clinical activity and tolerability of SL-401 (Tagraxofusp): recombinant diphtheria toxin and interleukin-3 in hematologic malignancies. Biomedicines, 7, pii: E6. doi: https://doi.org/10.3390/biomedicines7010006.
Appelbaum, F.R. & Bernstein, I.D. (2017) Gemtuzumab ozogamicin for acute myeloid leukemia. Blood, 130, 2373-2376.
Bill, M., Niekerk, B.V.K., Woll, P.S., Laine Herborg, L., Stidsholt Roug, A., Hokland, P. & Nederby, L. (2018) Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A-related cancer stem cell biology. Journal of Cellular and Molecular Medicine, 22, 2311-2318.
Bonnet, D. & Dick, J.E. (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 3, 730-737.
Bos, J.L., Toksoz, D., Marshall, C.J., Verlaan-de Vries, M., Veeneman, G.H., van der Eb, A.J., van Boom, J.H., Janssen, J.W. & Steenvoorden, A.C. (1985) Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. Nature, 315, 726-730.
Boyd, A.L., Aslostovar, L., Reid, J., Ye, W., Tanasijevic, B., Porras, D.P., Shapovalova, Z., Almakadi, M., Foley, R., Leber, B., Xenocostas, A. & Bhatia, M. (2018) Identification of chemotherapy-induced leukemic-regenerating cells reveals a transient vulnerability of human AML recurrence. Cancer Cell, 34, e485.
Brunetti, L., Gundry, M.C., Sorcini, D., Guzman, A.G., Huang, Y.H., Ramabadran, R., Gionfriddo, I., Mezzasoma, F., Milano, F., Nabet, B., Buckley, D.L., Kornblau, S.M., Lin, C.Y., Sportoletti, P., Martelli, M.P., Falini, B. & Goodell, M.A. (2018) Mutant NPM1 maintains the leukemic state through HOX expression. Cancer Cell, 34, e499.
Buick, R.N., Minden, M.D. & McCulloch, E.A. (1979) Self-renewal in culture of proliferative blast progenitor cells in acute myeloblastic leukemia. Blood, 54, 95-104.
Cancer Genome Atlas Research Network (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. New England Journal of Medicine, 368, 2059-2074.
Chen, J., Kao, Y.R., Sun, D., Todorova, T.I., Reynolds, D., Narayanagari, S.R., Montagna, C., Will, B., Verma, A. & Steidl, U. (2019) Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level. Nature Medicine, 25, 103-110.
Chesnais, V., Arcangeli, M.L., Delette, C., Rousseau, A., Guermouche, H., Lefevre, C., Bondu, S., Diop, M., Cheok, M., Chapuis, N., Legros, L., Raynaud, S., Willems, L., Bouscary, D., Lauret, E., Bernard, O.A., Kosmider, O., Pflumio, F. & Fontenay, M. (2017) Architectural and functional heterogeneity of hematopoietic stem/progenitor cells in non-del(5q) myelodysplastic syndromes. Blood, 129, 484-496.
Craddock, C., Quek, L., Goardon, N., Freeman, S., Siddique, S., Raghavan, M., Aztberger, A., Schuh, A., Grimwade, D., Ivey, A., Virgo, P., Hills, R., McSkeane, T., Arrazi, J., Knapper, S., Brookes, C., Davies, B., Price, A., Wall, K., Griffiths, M., Cavenagh, J., Majeti, R., Weissman, I., Burnett, A. & Vyas, P. (2013) Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia, 27, 1028-1036.
Crews, L.A., Balaian, L., Delos Santos, N.P., Leu, H.S., Court, A.C., Lazzari, E., Sadarangani, A., Zipeto, M.A., La Clair, J.J., Villa, R., Kulidjian, A., Storb, R., Morris, S.R., Ball, E.D., Burkart, M.D. & Jamieson, C.H.M. (2016) RNA splicing modulation selectively impairs leukemia stem cell maintenance in secondary human AML. Cell Stem Cell, 19, 599-612.
Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P.S., Rothenberg, M.E., Leyrat, A.A., Sim, S., Okamoto, J., Johnston, D.M., Qian, D., Zabala, M., Bueno, J., Neff, N.F., Wang, J., Shelton, A.A., Visser, B., Hisamori, S., Shimono, Y., van de Wetering, M., Clevers, H., Clarke, M.F. & Quake, S.R. (2011) Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nature Biotechnology, 29, 1120-1127.
Desai, P., Mencia-Trinchant, N., Savenkov, O., Simon, M.S., Cheang, G., Lee, S., Samuel, M., Ritchie, E.K., Guzman, M.L., Ballman, K.V., Roboz, G.J. & Hassane, D.C. (2018) Somatic mutations precede acute myeloid leukemia years before diagnosis. Nature Medicine, 24, 1015-1023.
Ebert, B.L. & Kronke, J. (2018) Inhibition of casein kinase 1 alpha in acute myeloid leukemia. New England Journal of Medicine, 379, 1873-1874.
Garg, S., Reyes-Palomares, A., He, L., Bergeron, A., Lavallee, V.P., Lemieux, S., Gendron, P., Rohde, C., Xia, J., Jagdhane, P., Muller-Tidow, C., Lipka, D.B., Imren, S., Humphries, R.K., Waskow, C., Vick, B., Jeremias, I., Richard-Carpentier, G., Hebert, J., Sauvageau, G., Zaugg, J., Barabe, F. & Pabst, C. (2019) Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML. Blood, https://doi.org/10.1182/blood.2018862383 [Epub ahead of print].
Garzon, R., Savona, M., Baz, R., Andreeff, M., Gabrail, N., Gutierrez, M., Savoie, L., Mau-Sorensen, P.M., Wagner-Johnston, N., Yee, K., Unger, T.J., Saint-Martin, J.R., Carlson, R., Rashal, T., Kashyap, T., Klebanov, B., Shacham, S., Kauffman, M. & Stone, R. (2017) A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Blood, 129, 3165-3174.
Gawad, C., Koh, W. & Quake, S.R. (2016) Single-cell genome sequencing: current state of the science. Nature Reviews Genetics, 17, 175-188.
Gelsi-Boyer, V., Trouplin, V., Adelaide, J., Bonansea, J., Cervera, N., Carbuccia, N., Lagarde, A., Prebet, T., Nezri, M., Sainty, D., Olschwang, S., Xerri, L., Chaffanet, M., Mozziconacci, M.J., Vey, N. & Birnbaum, D. (2009) Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. British Journal of Haematology, 145, 788-800.
Gentles, A.J., Plevritis, S.K., Majeti, R. & Alizadeh, A.A. (2010) Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA, 304, 2706-2715.
Giustacchini, A., Thongjuea, S., Barkas, N., Woll, P.S., Povinelli, B.J., Booth, C.A.G., Sopp, P., Norfo, R., Rodriguez-Meira, A., Ashley, N., Jamieson, L., Vyas, P., Anderson, K., Segerstolpe, A., Qian, H., Olsson-Stromberg, U., Mustjoki, S., Sandberg, R., Jacobsen, S.E.W. & Mead, A.J. (2017) Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nature Medicine, 23, 692-702.
Goardon, N., Marchi, E., Atzberger, A., Quek, L., Schuh, A., Soneji, S., Woll, P., Mead, A., Alford, K.A., Rout, R., Chaudhury, S., Gilkes, A., Knapper, S., Beldjord, K., Begum, S., Rose, S., Geddes, N., Griffiths, M., Standen, G., Sternberg, A., Cavenagh, J., Hunter, H., Bowen, D., Killick, S., Robinson, L., Price, A., Macintyre, E., Virgo, P., Burnett, A., Craddock, C., Enver, T., Jacobsen, S.E., Porcher, C. & Vyas, P. (2011) Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell, 19, 138-152.
Hanekamp, D., Cloos, J. & Schuurhuis, G.J. (2017) Leukemic stem cells: identification and clinical application. International Journal of Hematology, 105, 549-557.
Hanekamp, D., Denys, B., Kaspers, G.J.L., Te Marvelde, J.G., Schuurhuis, G.J., De Haas, V., De Moerloose, B., de Bont, E.S., Zwaan, C.M., de Jong, A., Depreter, B., Lammens, T., Philippe, J., Cloos, J. & van der Velden, V.H.J. (2018) Leukaemic stem cell load at diagnosis predicts the development of relapse in young acute myeloid leukaemia patients. British Journal of Haematology, 183, 512-516.
Hansen, M.C., Nederby, L., Kjeldsen, E., Petersen, M.A., Ommen, H.B. & Hokland, P. (2018) Case report: Exome sequencing identifies T-ALL with myeloid features as a IKZF1-struck early precursor T-cell malignancy. Leuk Res Rep, 9, 1-4.
Ho, T.C., LaMere, M., Stevens, B.M., Ashton, J.M., Myers, J.R., O'Dwyer, K.M., Liesveld, J.L., Mendler, J.H., Guzman, M., Morrissette, J.D., Zhao, J., Wang, E.S., Wetzler, M., Jordan, C.T. & Becker, M.W. (2016) Evolution of acute myelogenous leukemia stem cell properties after treatment and progression. Blood, 128, 1671-1678.
Jiang, Y.P., Liu, B.Y., Zheng, Q., Panuganti, S., Chen, R., Zhu, J., Mishra, M., Huang, J., Dao-Pick, T., Roy, S., Zhao, X., Lin, J., Banik, G., Hsi, E.D., Mandalam, R. & Junutula, J.R. (2018) CLT030, a leukemic stem cell-targeting CLL1 antibody-drug conjugate for treatment of acute myeloid leukemia. Blood Advances, 2, 1738-1749.
Kanda, Y., Hamaki, T., Yamamoto, R., Chizuka, A., Suguro, M., Matsuyama, T., Takezako, N., Miwa, A., Kami, M., Hirai, H. & Togawa, A. (2000) The clinical significance of CD34 expression in response to therapy of patients with acute myeloid leukemia: an overview of 2483 patients from 22 studies. Cancer, 88, 2529-2533.
Karamitros, D., Stoilova, B., Aboukhalil, Z., Hamey, F., Reinisch, A., Samitsch, M., Quek, L., Otto, G., Repapi, E., Doondeea, J., Usukhbayar, B., Calvo, J., Taylor, S., Goardon, N., Six, E., Pflumio, F., Porcher, C., Majeti, R., Gottgens, B. & Vyas, P. (2018) Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells. Nature Immunology, 19, 85-97.
Klco, J.M., Spencer, D.H., Miller, C.A., Griffith, M., Lamprecht, T.L., O'Laughlin, M., Fronick, C., Magrini, V., Demeter, R.T., Fulton, R.S., Eades, W.C., Link, D.C., Graubert, T.A., Walter, M.J., Mardis, E.R., Dipersio, J.F., Wilson, R.K. & Ley, T.J. (2014) Functional heterogeneity of genetically defined subclones in acute myeloid leukemia. Cancer Cell, 25, 379-392.
Ko, M., Huang, Y., Jankowska, A.M., Pape, U.J., Tahiliani, M., Bandukwala, H.S., An, J., Lamperti, E.D., Koh, K.P., Ganetzky, R., Liu, X.S., Aravind, L., Agarwal, S., Maciejewski, J.P. & Rao, A. (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature, 468, 839-843.
Kovtun, Y., Jones, G.E., Adams, S., Harvey, L., Audette, C.A., Wilhelm, A., Bai, C., Rui, L., Laleau, R., Liu, F., Ab, O., Setiady, Y., Yoder, N.C., Goldmacher, V.S., Chari, R.V.J., Pinkas, J. & Chittenden, T. (2018) A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Advances, 2, 848-858.
Kreso, A. & Dick, J.E. (2014) Evolution of the cancer stem cell model. Cell Stem Cell, 14, 275-291.
Laborda, E., Mazagova, M., Shao, S., Wang, X., Quirino, H., Woods, A.K., Hampton, E.N., Rodgers, D.T., Kim, C.H., Schultz, P.G. & Young, T.S. (2017) Development of a chimeric antigen receptor targeting C-type lectin-like molecule-1 for human acute myeloid leukemia. International Journal of Molecular Sciences, 18, pii: E2259.
Lagadinou, E.D., Sach, A., Callahan, K., Rossi, R.M., Neering, S.J., Minhajuddin, M., Ashton, J.M., Pei, S., Grose, V., O'Dwyer, K.M., Liesveld, J.L., Brookes, P.S., Becker, M.W. & Jordan, C.T. (2013) BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell, 12, 329-341.
Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M.A. & Dick, J.E. (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367, 645-648.
Lechman, E.R., Gentner, B., Ng, S.W., Schoof, E.M., van Galen, P., Kennedy, J.A., Nucera, S., Ciceri, F., Kaufmann, K.B., Takayama, N., Dobson, S.M., Trotman-Grant, A., Krivdova, G., Elzinga, J., Mitchell, A., Nilsson, B., Hermans, K.G., Eppert, K., Marke, R., Isserlin, R., Voisin, V., Bader, G.D., Zandstra, P.W., Golub, T.R., Ebert, B.L., Lu, J., Minden, M., Wang, J.C., Naldini, L. & Dick, J.E. (2016) miR-126 regulates distinct self-renewal outcomes in normal and malignant hematopoietic stem cells. Cancer Cell, 29, 214-228.
Leong, S.R., Sukumaran, S., Hristopoulos, M., Totpal, K., Stainton, S., Lu, E., Wong, A., Tam, L., Newman, R., Vuillemenot, B.R., Ellerman, D., Gu, C., Mathieu, M., Dennis, M.S., Nguyen, A., Zheng, B., Zhang, C., Lee, G., Chu, Y.W., Prell, R.A., Lin, K., Laing, S.T. & Polson, A.G. (2017) An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia. Blood, 129, 609-618.
Levesque, J.P., Hendy, J., Takamatsu, Y., Simmons, P.J. & Bendall, L.J. (2003) Disruption of the CXCR45/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. Journal of Clinical Investigation, 111, 187-196.
Liu, N., Song, J., Xie, Y., Wang, X.L., Rong, B., Man, N., Zhang, M.M., Zhang, Q., Gao, F.F., Du, M.R., Zhang, Y., Shen, J., Xu, C.H., Hu, C.L., Wu, J.C., Liu, P., Zhang, Y.L., Xie, Y.Y., Liu, P., Huang, J.Y., Huang, Q.H., Lan, F., Shen, S., Nimer, S.D., Chen, Z., Chen, S.J., Roeder, R.G., Wang, L. & Sun, X.J. (2019) Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. Proceedings of the National Academy of Sciences, USA, 116, 890-899.
Lu, H., Zhou, Q., Deshmukh, V., Phull, H., Ma, J., Tardif, V., Naik, R.R., Bouvard, C., Zhang, Y., Choi, S., Lawson, B.R., Zhu, S., Kim, C.H. & Schultz, P.G. (2014) Targeting human C-type lectin-like molecule-1 (CLL1) with a bispecific antibody for immunotherapy of acute myeloid leukemia. Angewandte Chemie (International ed. in English), 53, 9841-9845.
Luis, T.C., Ichii, M., Brugman, M.H., Kincade, P. & Staal, F.J. (2012) Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development. Leukemia, 26, 414-421.
Mardis, E.R., Ding, L., Dooling, D.J., Larson, D.E., McLellan, M.D., Chen, K., Koboldt, D.C., Fulton, R.S., Delehaunty, K.D., McGrath, S.D., Fulton, L.A., Locke, D.P., Magrini, V.J., Abbott, R.M., Vickery, T.L., Reed, J.S., Robinson, J.S., Wylie, T., Smith, S.M., Carmichael, L., Eldred, J.M., Harris, C.C., Walker, J., Peck, J.B., Du, F., Dukes, A.F., Sanderson, G.E., Brummett, A.M., Clark, E., McMichael, J.F., Meyer, R.J., Schindler, J.K., Pohl, C.S., Wallis, J.W., Shi, X., Lin, L., Schmidt, H., Tang, Y., Haipek, C., Wiechert, M.E., Ivy, J.V., Kalicki, J., Elliott, G., Ries, R.E., Payton, J.E., Westervelt, P., Tomasson, M.H., Watson, M.A., Baty, J., Heath, S., Shannon, W.D., Nagarajan, R., Link, D.C., Walter, M.J., Graubert, T.A., DiPersio, J.F., Wilson, R.K. & Ley, T.J. (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. New England Journal of Medicine, 361, 1058-1066.
Martelli, A.M., Evangelisti, C., Chiarini, F. & McCubrey, J.A. (2010) The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget, 1, 89-103.
Meyer, S.E., Muench, D.E., Rogers, A.M., Newkold, T.J., Orr, E., O'Brien, E., Perentesis, J.P., Doench, J.G., Lal, A., Morris, P.J., Thomas, C.J., Lieberman, J., McGlinn, E., Aronow, B.J., Salomonis, N. & Grimes, H.L. (2018) miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential. Journal of Experimental Medicine, 215, 2115-2136.
Moore, M.A., Williams, N. & Metcalf, D. (1973) In vitro colony formation by normal and leukemic human hematopoietic cells: characterization of the colony-forming cells. Journal of the National Cancer Institute, 50, 603-623.
Mora-Jensen, H., Jendholm, J., Rapin, N., Andersen, M.K., Roug, A.S., Bagger, F.O., Bullinger, L., Winther, O., Borregaard, N., Porse, B.T. & Theilgaard-Monch, K. (2015) Cellular origin of prognostic chromosomal aberrations in AML patients. Leukemia, 29, 1785-1789.
Ng, S.W., Mitchell, A., Kennedy, J.A., Chen, W.C., McLeod, J., Ibrahimova, N., Arruda, A., Popescu, A., Gupta, V., Schimmer, A.D., Schuh, A.C., Yee, K.W., Bullinger, L., Herold, T., Gorlich, D., Buchner, T., Hiddemann, W., Berdel, W.E., Wormann, B., Cheok, M., Preudhomme, C., Dombret, H., Metzeler, K., Buske, C., Lowenberg, B., Valk, P.J., Zandstra, P.W., Minden, M.D., Dick, J.E. & Wang, J.C. (2016) A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature, 540, 433-437.
Nowell, P.C. (1976) The clonal evolution of tumor cell populations. Science, 194, 23-28.
Pearce, D.J., Taussig, D., Zibara, K., Smith, L.L., Ridler, C.M., Preudhomme, C., Young, B.D., Rohatiner, A.Z., Lister, T.A. & Bonnet, D. (2006) AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML. Blood, 107, 1166-1173.
Peled, A., Petit, I., Kollet, O., Magid, M., Ponomaryov, T., Byk, T., Nagler, A., Ben-Hur, H., Many, A., Shultz, L., Lider, O., Alon, R., Zipori, D. & Lapidot, T. (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR57. Science, 283, 845-848.
Peled, A., Kollet, O., Ponomaryov, T., Petit, I., Franitza, S., Grabovsky, V., Slav, M.M., Nagler, A., Lider, O., Alon, R., Zipori, D. & Lapidot, T. (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice. Blood, 95, 3289-3296.
Pellegrino, M., Sciambi, A., Treusch, S., Durruthy-Durruthy, R., Gokhale, K., Jacob, J., Chen, T.X., Geis, J.A., Oldham, W., Matthews, J., Kantarjian, H., Futreal, P.A., Patel, K., Jones, K.W., Takahashi, K. & Eastburn, D.J. (2018) High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics. Genome Research, 28, 1345-1352.
Pemovska, T., Kontro, M., Yadav, B., Edgren, H., Eldfors, S., Szwajda, A., Almusa, H., Bespalov, M.M., Ellonen, P., Elonen, E., Gjertsen, B.T., Karjalainen, R., Kulesskiy, E., Lagstrom, S., Lehto, A., Lepisto, M., Lundan, T., Majumder, M.M., Marti, J.M., Mattila, P., Murumagi, A., Mustjoki, S., Palva, A., Parsons, A., Pirttinen, T., Ramet, M.E., Suvela, M., Turunen, L., Vastrik, I., Wolf, M., Knowles, J., Aittokallio, T., Heckman, C.A., Porkka, K., Kallioniemi, O. & Wennerberg, K. (2013) Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discovery, 3, 1416-1429.
Pollyea, D.A. & Jordan, C.T. (2017) Therapeutic targeting of acute myeloid leukemia stem cells. Blood, 129, 1627-1635.
Pollyea, D.A., Stevens, B.M., Jones, C.L., Winters, A., Pei, S., Minhajuddin, M., D'Alessandro, A., Culp-Hill, R., Riemondy, K.A., Gillen, A.E., Hesselberth, J.R., Abbott, D., Schatz, D., Gutman, J.A., Purev, E., Smith, C. & Jordan, C.T. (2018) Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia. Nature Medicine, 24, 1859-1866.
Quek, L., Otto, G.W., Garnett, C., Lhermitte, L., Karamitros, D., Stoilova, B., Lau, I.J., Doondeea, J., Usukhbayar, B., Kennedy, A., Metzner, M., Goardon, N., Ivey, A., Allen, C., Gale, R., Davies, B., Sternberg, A., Killick, S., Hunter, H., Cahalin, P., Price, A., Carr, A., Griffiths, M., Virgo, P., Mackinnon, S., Grimwade, D., Freeman, S., Russell, N., Craddock, C., Mead, A., Peniket, A., Porcher, C. & Vyas, P. (2016) Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. Journal of Experimental Medicine, 213, 1513-1535.
Quek, L., David, M.D., Kennedy, A., Metzner, M., Amatangelo, M., Shih, A., Stoilova, B., Quivoron, C., Heiblig, M., Willekens, C., Saada, V., Alsafadi, S., Vijayabaskar, M.S., Peniket, A., Bernard, O.A., Agresta, S., Yen, K., MacBeth, K., Stein, E., Vassiliou, G.S., Levine, R., De Botton, S., Thakurta, A., Penard-Lacronique, V. & Vyas, P. (2018) Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib. Nature Medicine, 24, 1167-1177.
Rahmani, M., Aust, M.M., Attkisson, E., Williams, D.C. Jr, Ferreira-Gonzalez, A. & Grant, S. (2013) Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism. Cancer Research, 73, 1340-1351.
Reinisch, A., Thomas, D., Corces, M.R., Zhang, X., Gratzinger, D., Hong, W.J., Schallmoser, K., Strunk, D. & Majeti, R. (2016) A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells. Nature Medicine, 22, 812-821.
Richard-Carpentier, G. & Sauvageau, G. (2017) Bringing a leukemic stem cell gene signature into clinics: are we there yet? Cell Stem Cell, 20, 300-301.
Rodriguez-Meira, A., Buck, G., Clark, S.A., Povinelli, B.J., Alcolea, V., Louka, E., McGowan, S., Hamblin, A., Sousos, N., Barkas, N., Giustacchini, A., Psaila, B., Jacobsen, S.E.W., Thongjuea, S. & Mead, A.J. (2019) Unravelling intratumoral heterogeneity through high-sensitivity single-cell mutational analysis and parallel RNA sequencing. Molecular Cell, 73, e1298.
Shlush, L.I., Mitchell, A., Heisler, L., Abelson, S., Ng, S.W.K., Trotman-Grant, A., Medeiros, J.J.F., Rao-Bhatia, A., Jaciw-Zurakowsky, I., Marke, R., McLeod, J.L., Doedens, M., Bader, G., Voisin, V., Xu, C., McPherson, J.D., Hudson, T.J., Wang, J.C.Y., Minden, M.D. & Dick, J.E. (2017) Tracing the origins of relapse in acute myeloid leukaemia to stem cells. Nature, 547, 104-108.
Simonsen, A.T., Hansen, M.C., Kjeldsen, E., Moller, P.L., Hindkjaer, J.J., Hokland, P. & Aggerholm, A. (2018) Systematic evaluation of signal-to-noise ratio in variant detection from single cell genome multiple displacement amplification and exome sequencing. BMC Genomics, 19, 681.
Smith, C.C., Paguirigan, A., Jeschke, G.R., Lin, K.C., Massi, E., Tarver, T., Chin, C.S., Asthana, S., Olshen, A., Travers, K.J., Wang, S., Levis, M.J., Perl, A.E., Radich, J.P. & Shah, N.P. (2017) Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell analysis. Blood, 130, 48-58.
Sutherland, H.J., Eaves, C.J., Eaves, A.C., Dragowska, W. & Lansdorp, P.M. (1989) Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood, 74, 1563-1570.
Sutherland, H.J., Lansdorp, P.M., Henkelman, D.H., Eaves, A.C. & Eaves, C.J. (1990) Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proceedings of the National Academy of Sciences, USA, 87, 3584-3588.
Tashiro, H., Sauer, T., Shum, T., Parikh, K., Mamonkin, M., Omer, B., Rouce, R.H., Lulla, P., Rooney, C.M., Gottschalk, S. & Brenner, M.K. (2017) Treatment of acute myeloid leukemia with T cells expressing chimeric antigen receptors directed to C-type lectin-like molecule 1. Molecular Therapy, 25, 2202-2213.
Taussig, D.C., Vargaftig, J., Miraki-Moud, F., Griessinger, E., Sharrock, K., Luke, T., Lillington, D., Oakervee, H., Cavenagh, J., Agrawal, S.G., Lister, T.A., Gribben, J.G. & Bonnet, D. (2010) Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction. Blood, 115, 1976-1984.
Terwijn, M., Zeijlemaker, W., Kelder, A., Rutten, A.P., Snel, A.N., Scholten, W.J., Pabst, T., Verhoef, G., Lowenberg, B., Zweegman, S., Ossenkoppele, G.J. & Schuurhuis, G.J. (2014) Leukemic stem cell frequency: a strong biomarker for clinical outcome in acute myeloid leukemia. PLoS One, 9, e107587.
Thomas, D. & Majeti, R. (2017) Biology and relevance of human acute myeloid leukemia stem cells. Blood, 129, 1577-1585.
Tyner, J.W., Tognon, C.E., Bottomly, D., Wilmot, B., Kurtz, S.E., Savage, S.L., Long, N., Schultz, A.R., Traer, E., Abel, M., Agarwal, A., Blucher, A., Borate, U., Bryant, J., Burke, R., Carlos, A., Carpenter, R., Carroll, J., Chang, B.H., Coblentz, C., d'Almeida, A., Cook, R., Danilov, A., Dao, K.T., Degnin, M., Devine, D., Dibb, J.,Edwards, D.K.T., Eide, C.A., English, I., Glover, J., Henson, R., Ho, H., Jemal, A., Johnson, K., Johnson, R., Junio, B., Kaempf, A., Leonard, J., Lin, C., Liu, S.Q., Lo, P., Loriaux, M.M., Luty, S., Macey, T., MacManiman, J., Martinez, J., Mori, M., Nelson, D., Nichols, C., Peters, J., Ramsdill, J., Rofelty, A., Schuff, R., Searles, R., Segerdell, E., Smith, R.L., Spurgeon, S.E., Sweeney, T., Thapa, A., Visser, C., Wagner, J., Watanabe-Smith, K., Werth, K., Wolf, J., White, L., Yates, A., Zhang, H., Cogle, C.R., Collins, R.H., Connolly, D.C., Deininger, M.W., Drusbosky, L., Hourigan, C.S., Jordan, C.T., Kropf, P., Lin, T.L., Martinez, M.E., Medeiros, B.C., Pallapati, R.R., Pollyea, D.A., Swords, R.T., Watts, J.M., Weir, S.J., Wiest, D.L., Winters, R.M., McWeeney, S.K. & Druker, B.J. (2018) Functional genomic landscape of acute myeloid leukaemia. Nature, 562, 526-531.
Valent, P., Bonnet, D., De Maria, R., Lapidot, T., Copland, M., Melo, J.V., Chomienne, C., Ishikawa, F., Schuringa, J.J., Stassi, G., Huntly, B., Herrmann, H., Soulier, J., Roesch, A., Schuurhuis, G.J., Wohrer, S., Arock, M., Zuber, J., Cerny-Reiterer, S., Johnsen, H.E., Andreeff, M. & Eaves, C. (2012) Cancer stem cell definitions and terminology: the devil is in the details. Nature Reviews Cancer, 12, 767-775.
van Galen, P., Mbong, N., Kreso, A., Schoof, E.M., Wagenblast, E., Ng, S.W.K., Krivdova, G., Jin, L., Nakauchi, H. & Dick, J.E. (2018) Integrated stress response activity marks stem cells in normal hematopoiesis and leukemia. Cell Reports, 25, e1105.
van Rhenen, A., Moshaver, B., Kelder, A., Feller, N., Nieuwint, A.W., Zweegman, S., Ossenkoppele, G.J. & Schuurhuis, G.J. (2007a) Aberrant marker expression patterns on the CD34+CD38- stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission. Leukemia, 21, 1700-1707.
van Rhenen, A., van Dongen, G.A., Kelder, A., Rombouts, E.J., Feller, N., Moshaver, B., Stigter-van Walsum, M., Zweegman, S., Ossenkoppele, G.J. & Jan Schuurhuis, G. (2007b) The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood, 110, 2659-2666.
Walter, R.B., Appelbaum, F.R., Estey, E.H. & Bernstein, I.D. (2012) Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood, 119, 6198-6208.
Wang, Y., Krivtsov, A.V., Sinha, A.U., North, T.E., Goessling, W., Feng, Z., Zon, L.I. & Armstrong, S.A. (2010) The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science, 327, 1650-1653.
Wang, K., Sanchez-Martin, M., Wang, X., Knapp, K.M., Koche, R., Vu, L., Nahas, M.K., He, J., Hadler, M., Stein, E.M., Tallman, M.S., Donahue, A.L., Frampton, G.M., Lipson, D., Roels, S., Stephens, P.J., Sanford, E.M., Brennan, T., Otto, G.A., Yelensky, R., Miller, V.A., Kharas, M.G., Levine, R.L., Ferrando, A., Armstrong, S.A. & Krivtsov, A.V. (2017) Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias. Leukemia, 31, 151-158.
Wang, A.Y., Weiner, H., Green, M., Chang, H., Fulton, N., Larson, R.A., Odenike, O., Artz, A.S., Bishop, M.R., Godley, L.A., Thirman, M.J., Kosuri, S., Churpek, J.E., Curran, E., Pettit, K., Stock, W. & Liu, H. (2018a) A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. Journal of Hematology and Oncology, 11, 4.
Wang, J., Chen, S., Xiao, W., Li, W., Wang, L., Yang, S., Wang, W., Xu, L., Liao, S., Liu, W., Wang, Y., Liu, N., Zhang, J., Xia, X., Kang, T., Chen, G., Cai, X., Yang, H., Zhang, X., Lu, Y. & Zhou, P. (2018b) CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia. Journal of Hematology and Oncology, 11, 7.
Woll, P.S., Kjallquist, U., Chowdhury, O., Doolittle, H., Wedge, D.C., Thongjuea, S., Erlandsson, R., Ngara, M., Anderson, K., Deng, Q., Mead, A.J., Stenson, L., Giustacchini, A., Duarte, S., Giannoulatou, E., Taylor, S., Karimi, M., Scharenberg, C., Mortera-Blanco, T., Macaulay, I.C., Clark, S.A., Dybedal, I., Josefsen, D., Fenaux, P., Hokland, P., Holm, M.S., Cazzola, M., Malcovati, L., Tauro, S., Bowen, D., Boultwood, J., Pellagatti, A., Pimanda, J.E., Unnikrishnan, A., Vyas, P., Gohring, G., Schlegelberger, B., Tobiasson, M., Kvalheim, G., Constantinescu, S.N., Nerlov, C., Nilsson, L., Campbell, P.J., Sandberg, R., Papaemmanuil, E., Hellstrom-Lindberg, E., Linnarsson, S. & Jacobsen, S.E. (2014) Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 25, 794-808.
Zeijlemaker, W., Kelder, A., Wouters, R., Valk, P.J.M., Witte, B.I., Cloos, J., Ossenkoppele, G.J. & Schuurhuis, G.J. (2015) Absence of leukaemic CD34(+) cells in acute myeloid leukaemia is of high prognostic value: a longstanding controversy deciphered. British Journal of Haematology, 171, 227-238.
Zeijlemaker, W., Grob, T., Meijer, R., Hanekamp, D., Kelder, A., Carbaat-Ham, J.C., Oussoren-Brockhoff, Y.J.M., Snel, A.N., Veldhuizen, D., Scholten, W.J., Maertens, J., Breems, D.A., Pabst, T., Manz, M.G., van der Velden, V.H.J., Slomp, J., Preijers, F., Cloos, J., van de Loosdrecht, A.A., Lowenberg, B., Valk, P.J.M., Jongen-Lavrencic, M., Ossenkoppele, G.J. & Schuurhuis, G.J. (2018) CD34(+)CD38(-) leukemic stem cell frequency to predict outcome in acute myeloid leukemia. Leukemia, 33, 1102-1112.
Zhao, X., Singh, S., Pardoux, C., Zhao, J., Hsi, E.D., Abo, A. & Korver, W. (2010) Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia. Haematologica, 95, 71-78.
Zhou, F., Liu, Y., Rohde, C., Pauli, C., Gerloff, D., Kohn, M., Misiak, D., Baumer, N., Cui, C., Gollner, S., Oellerich, T., Serve, H., Garcia-Cuellar, M.P., Slany, R., Maciejewski, J.P., Przychodzen, B., Seliger, B., Klein, H.U., Bartenhagen, C., Berdel, W.E., Dugas, M., Taketo, M.M., Farouq, D., Schwartz, S., Regev, A., Hebert, J., Sauvageau, G., Pabst, C., Huttelmaier, S. & Muller-Tidow, C. (2017) AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Nature Cell Biology, 19, 844-855.