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Leukemic and Lymphoid Stem Cells

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Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology

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Abstract

Cancer cell heterogeneity is a feature of nearly all cancers and can be related to three major influences: (1) genetic and epigenetic heterogeneity due to clonal evolution/collapse; (2) microenvironmental influences; and (3) the underlying tissue hierarchy from which the tumor arises. Ongoing studies in whole genome sequencing and of the bone marrow, splenic and lymph node microenvironments demonstrate their contributions to tumor heterogeneity. In this chapter we will focus on the role of the hematopoietic hierarchy in blood cancer cellular heterogeneity; one of the most studied systems in mouse and human. Observations that myeloid and lymphoid malignancies harbor rare relatively quiescent therapy resistant cell populations date back over 30 years. Early studies in chronic myelogenous leukemia were consistent with a disease origin in the hematopoietic stem cell and subsequent studies have confirmed these findings. The publication by Bonnet et al. in 1994 offered the first prospective assessment of human cancer stem cell populations and established acute myeloid leukemia (AML) as a model system. In the intervening years, new technologies have allowed a continued reassessment of cancer stem cell populations in AML, myelodysplastic syndromes, multiple myeloma and acute lymphoblastic leukemia. While these studies have confirmed the existence of the rare cells capable of recapitulating the malignancy on transplantation, they have also identified considerable inter- and intra-patient heterogeneity with conflicting results on the ability to identify potential cancer stem cells using surface antigen profiles alone. Novel xenotransplantation models, whole genome sequencing and other technologies offer the tools to further refine this model in hematologic malignancies and develop rational therapies to target leukemia stem cells.

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References

  • Abrahamsson AE, Geron I, Gotlib J, Dao KH, Barroga CF, Newton IG, Giles FJ, Durocher J, Creusot RS, Karimi M, Jones C, Zehnder JL, Keating A, Negrin RS, Weissman IL, Jamieson CH (2009) Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci USA 106(10):3925–3929

    PubMed Central  CAS  PubMed  Google Scholar 

  • Agarwal JR, Wang Q, Tanno T, Rasheed Z, Merchant A, Ghosh N, Borrello I, Huff CA, Parhami F, Matsui W (2014) Activation of liver X receptors inhibits hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma. Mol Cancer Ther 13(7):1873–1881

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ahuja H, Bar-Eli M, Advani SH, Benchimol S, Cline MJ (1989) Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. Proc Natl Acad Sci USA 86(17):6783–6787

    PubMed Central  CAS  PubMed  Google Scholar 

  • Aigner M, Feulner J, Schaffer S, Kischel R, Kufer P, Schneider K, Henn A, Rattel B, Friedrich M, Baeuerle PA, Mackensen A, Krause SW (2013) T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Leukemia 27(5):1107–1115

    CAS  PubMed  Google Scholar 

  • Askmyr M, Agerstam H, Hansen N, Gordon S, Arvanitakis A, Rissler M, Juliusson G, Richter J, Jaras M, Fioretos T (2013) Selective killing of candidate AML stem cells by antibody targeting of IL1RAP. Blood 121(18):3709–3713

    CAS  PubMed  Google Scholar 

  • Bakker AB, van den Oudenrijn S, Bakker AQ, Feller N, van Meijer M, Bia JA, Jongeneelen MA, Visser TJ, Bijl N, Geuijen CA, Marissen WE, Radosevic K, Throsby M, Schuurhuis GJ, Ossenkoppele GJ, de Kruif J, Goudsmit J, Kruisbeek AM (2004) C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia. Cancer Res 64(22):8443–8450

    CAS  PubMed  Google Scholar 

  • Barabe F, Kennedy JA, Hope KJ, Dick JE (2007) Modeling the initiation and progression of human acute leukemia in mice. Science 316(5824):600–604

    CAS  PubMed  Google Scholar 

  • Barlow JL, Drynan LF, Hewett DR, Holmes LR, Lorenzo-Abalde S, Lane AL, Jolin HE, Pannell R, Middleton AJ, Wong SH, Warren AJ, Wainscoat JS, Boultwood J, McKenzie AN (2010) A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med 16(1):59–66

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL (2011) Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 364(26):2496–2506

    PubMed Central  CAS  PubMed  Google Scholar 

  • Bergsagel DE, Valeriote FA (1968) Growth characteristics of a mouse plasma cell tumor. Cancer Res 28(11):2187–2196

    CAS  PubMed  Google Scholar 

  • Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K (2011) Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 29(4):369–377

    CAS  PubMed  Google Scholar 

  • Cancer Genome Atlas Research N (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074

    Google Scholar 

  • Castor A, Nilsson L, Astrand-Grundstrom I, Buitenhuis M, Ramirez C, Anderson K, Strombeck B, Garwicz S, Bekassy AN, Schmiegelow K, Lausen B, Hokland P, Lehmann S, Juliusson G, Johansson B, Jacobsen SE (2005) Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med 11(6):630–637

    CAS  PubMed  Google Scholar 

  • Chaidos A, Barnes CP, Cowan G, May PC, Melo V, Hatjiharissi E, Papaioannou M, Harrington H, Doolittle H, Terpos E, Dimopoulos M, Abdalla S, Yarranton H, Naresh K, Foroni L, Reid A, Rahemtulla A, Stumpf M, Roberts I, Karadimitris A (2013) Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma. Blood 121(2):318–328

    CAS  PubMed  Google Scholar 

  • Chou FS, Wunderlich M, Griesinger A, Mulloy JC (2011) N-Ras(G12D) induces features of stepwise transformation in preleukemic human umbilical cord blood cultures expressing the AML1-ETO fusion gene. Blood 117(7):2237–2240

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cobaleda C, Gutierrez-Cianca N, Perez-Losada J, Flores T, Garcia-Sanz R, Gonzalez M, Sanchez-Garcia I (2000) A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood 95(3):1007–1013

    CAS  PubMed  Google Scholar 

  • Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ (2011) Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest 121(1):396–409

    PubMed Central  CAS  PubMed  Google Scholar 

  • Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R (2014) Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci USA 111(7):2548–2553

    PubMed Central  CAS  PubMed  Google Scholar 

  • Cox CV, Evely RS, Oakhill A, Pamphilon DH, Goulden NJ, Blair A (2004) Characterization of acute lymphoblastic leukemia progenitor cells. Blood 104(9):2919–2925

    CAS  PubMed  Google Scholar 

  • Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL (2003) Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 17(24):3029–3035

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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(5):1028–1036

    CAS  PubMed  Google Scholar 

  • Dai Y, Guzman ML, Chen S, Wang L, Yeung SK, Pei XY, Dent P, Jordan CT, Grant S (2010) The NF (Nuclear factor)-kappaB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells. Br J Haematol 151(1):70–83

    PubMed Central  CAS  PubMed  Google Scholar 

  • Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6(224):224ra225

    Google Scholar 

  • de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR (1982) A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 300(5894):765–767

    PubMed  Google Scholar 

  • Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID (2010) Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 16(2):232–236

    PubMed Central  CAS  PubMed  Google Scholar 

  • Dick JE, Magli MC, Huszar D, Phillips RA, Bernstein A (1985) Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell 42(1):71–79

    CAS  PubMed  Google Scholar 

  • Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2(5):561–566

    CAS  PubMed  Google Scholar 

  • Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA, Investigators I (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355(23):2408–2417

    CAS  PubMed  Google Scholar 

  • Dutour A, Marin V, Pizzitola I, Valsesia-Wittmann S, Lee D, Yvon E, Finney H, Lawson A, Brenner M, Biondi A, Biagi E, Rousseau R (2012) In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33 acute myeloid leukemia. Adv Hematol 2012:683065

    PubMed Central  CAS  PubMed  Google Scholar 

  • Eisterer W, Jiang X, Christ O, Glimm H, Lee KH, Pang E, Lambie K, Shaw G, Holyoake TL, Petzer AL, Auewarakul C, Barnett MJ, Eaves CJ, Eaves AC (2005) Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia 19(3):435–441

    CAS  PubMed  Google Scholar 

  • Ema H, Sudo K, Seita J, Matsubara A, Morita Y, Osawa M, Takatsu K, Takaki S, Nakauchi H (2005) Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice. Dev Cell 8(6):907–914

    CAS  PubMed  Google Scholar 

  • Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, Metzeler KH, Poeppl A, Ling V, Beyene J, Canty AJ, Danska JS, Bohlander SK, Buske C, Minden MD, Golub TR, Jurisica I, Ebert BL, Dick JE (2011) Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17(9):1086–1093

    CAS  PubMed  Google Scholar 

  • Fialkow PJ, Jacobson RJ, Papayannopoulou T (1977) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med 63(1):125–130

    CAS  PubMed  Google Scholar 

  • Gentles AJ, Plevritis SK, Majeti R, Alizadeh AA (2010) Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. Jama 304(24):2706–2715

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gibbs KD Jr, Jager A, Crespo O, Goltsev Y, Trejo A, Richard CE, Nolan GP (2012) Decoupling of tumor-initiating activity from stable immunophenotype in HoxA9-Meis1-driven AML. Cell Stem Cell 10(2):210–217

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, Carroll M, Danet-Desnoyers G, Scholler J, Grupp SA, June CH, Kalos M (2014) Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 123(15):2343–2354

    PubMed Central  CAS  PubMed  Google Scholar 

  • Goardon N, Marchi E, Atzberger A, Quek L, Schuh A, Soneji S, Woll P, Mead A, Alford KA, 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 SE, Porcher C, Vyas P (2011) Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell 19(1):138–152

    CAS  PubMed  Google Scholar 

  • Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, Jordan CT (2001a) Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 98(8):2301–2307

    CAS  PubMed  Google Scholar 

  • Guzman ML, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, Phillips GL, Jordan CT (2001b) Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells. Blood 97(7):2177–2179

    CAS  PubMed  Google Scholar 

  • Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT (2005) The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood 105(11):4163–4169

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    CAS  PubMed  Google Scholar 

  • Hanoun M, Zhang D, Mizoguchi T, Pinho S, Pierce H, Kunisaki Y, Lacombe J, Armstrong SA, Duhrsen U, Frenette PS (2014) Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell 15(3):365–375

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hartwell KA, Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Jaras M, Puram R, Dancik V, Al-Shahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh JH, Steensma DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MA, Scadden DT, Schreiber SL, Ebert BL, Golub TR (2013) Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol 9(12):840–848

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hassane DC, Guzman ML, Corbett C, Li X, Abboud R, Young F, Liesveld JL, Carroll M, Jordan CT (2008) Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data. Blood 111(12):5654–5662

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hassane DC, Sen S, Minhajuddin M, Rossi RM, Corbett CA, Balys M, Wei L, Crooks PA, Guzman ML, Jordan CT (2010) Chemical genomic screening reveals synergism between parthenolide and inhibitors of the PI-3 kinase and mTOR pathways. Blood 116(26):5983–5990

    CAS  PubMed  Google Scholar 

  • Hehner SP, Hofmann TG, Droge W, Schmitz ML (1999) The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex. J Immunol 163(10):5617–5623

    CAS  PubMed  Google Scholar 

  • Ho TCL, O’Dwyer K, Mendler J, Liesveld J, Wetzler M, Wang ES, Guzman M, Jordan C, Becker MW (2013) Evolution of acute myelogenous leukemia stem cell properties following treatment and progression. Blood 122(21)

    Google Scholar 

  • Holyoake T, Jiang X, Eaves C, Eaves A (1999) Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood 94(6):2056–2064

    CAS  PubMed  Google Scholar 

  • Hosen N, Park CY, Tatsumi N, Oji Y, Sugiyama H, Gramatzki M, Krensky AM, Weissman IL (2007) CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci USA 104(26):11008–11013

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hosen N, Matsuoka Y, Kishida S, Nakata J, Mizutani Y, Hasegawa K, Mugitani A, Ichihara H, Aoyama Y, Nishida S, Tsuboi A, Fujiki F, Tatsumi N, Nakajima H, Hino M, Kimura T, Yata K, Abe M, Oka Y, Oji Y, Kumanogoh A, Sugiyama H (2012) CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients. Leukemia 26(9):2135–2141

    CAS  PubMed  Google Scholar 

  • Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR, Akashi K, Gilliland DG (2004) MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6(6):587–596

    CAS  PubMed  Google Scholar 

  • Hystad ME, Myklebust JH, Bo TH, Sivertsen EA, Rian E, Forfang L, Munthe E, Rosenwald A, Chiorazzi M, Jonassen I, Staudt LM, Smeland EB (2007) Characterization of early stages of human B cell development by gene expression profiling. J Immunol 179(6):3662–3671

    CAS  PubMed  Google Scholar 

  • Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, Nakamura R, Tanaka T, Tomiyama H, Saito N, Fukata M, Miyamoto T, Lyons B, Ohshima K, Uchida N, Taniguchi S, Ohara O, Akashi K, Harada M, Shultz LD (2007) Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol 25(11):1315–1321

    CAS  PubMed  Google Scholar 

  • Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, Heike T, Nakahata T (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100(9):3175–3182

    CAS  PubMed  Google Scholar 

  • Iwamoto C, Takenaka K, Urata S, Yamauchi T, Shima T, Kuriyama T, Daitoku S, Saito Y, Miyamoto T, Iwasaki H, Kitabayashi I, Itoh K, Kishimoto J, Kohda D, Matozaki T, Akashi K (2014) The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment. Exp Hematol 42(3):163–171, e161

    CAS  PubMed  Google Scholar 

  • Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, Gotlib J, Li K, Manz MG, Keating A, Sawyers CL, Weissman IL (2004) Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 351(7):657–667

    CAS  PubMed  Google Scholar 

  • Jan M, Chao MP, Cha AC, Alizadeh AA, Gentles AJ, Weissman IL, Majeti R (2011) Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker. Proc Natl Acad Sci USA 108(12):5009–5014

    PubMed Central  CAS  PubMed  Google Scholar 

  • Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, Majeti R (2012) Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci Transl Med 4(149):149ra118

    PubMed Central  PubMed  Google Scholar 

  • Jordan CT, Lemischka IR (1990) Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev 4(2):220–232

    CAS  PubMed  Google Scholar 

  • Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM, Phillips GL (2000) The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14(10):1777–1784

    CAS  PubMed  Google Scholar 

  • Jorgensen HG, Holyoake TL (2007) Characterization of cancer stem cells in chronic myeloid leukaemia. Biochem Soc Trans 35(Pt 5):1347–1351

    CAS  PubMed  Google Scholar 

  • Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M (2014) Positive feedback between NF-kappaB and TNF-alpha promotes leukemia-initiating cell capacity. J Clin Invest 124(2):528–542

    PubMed Central  CAS  PubMed  Google Scholar 

  • Kerbauy DM, Lesnikov V, Torok-Storb B, Bryant E, Deeg HJ (2004) Engraftment of distinct clonal MDS-derived hematopoietic precursors in NOD/SCID-beta2-microglobulin-deficient mice after intramedullary transplantation of hematopoietic and stromal cells. Blood 104(7):2202–2203

    CAS  PubMed  Google Scholar 

  • Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121(7):1109–1121

    CAS  PubMed  Google Scholar 

  • Kikushige Y, Miyamoto T (2013) TIM-3 as a novel therapeutic target for eradicating acute myelogenous leukemia stem cells. Int J Hematol 98(6):627–633

    CAS  PubMed  Google Scholar 

  • Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 442(7104):818–822

    CAS  PubMed  Google Scholar 

  • Krivtsov AV, Figueroa ME, Sinha AU, Stubbs MC, Feng Z, Valk PJ, Delwel R, Dohner K, Bullinger L, Kung AL, Melnick AM, Armstrong SA (2013) Cell of origin determines clinically relevant subtypes of MLL-rearranged AML. Leukemia 27(4):852–860

    CAS  PubMed  Google Scholar 

  • Kroeger H, Jelinek J, Estecio MR, He R, Kondo K, Chung W, Zhang L, Shen L, Kantarjian HM, Bueso-Ramos CE, Issa JP (2008) Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. Blood 112(4):1366–1373

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, Ashton JM, Pei S, Grose V, O’Dwyer KM, Liesveld JL, Brookes PS, Becker MW, Jordan CT (2013) BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell 12(3):329–341

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648

    CAS  PubMed  Google Scholar 

  • Liu Y, Cheng H, Gao S, Lu X, He F, Hu L, Hou D, Zou Z, Li Y, Zhang H, Xu J, Kang L, Wang Q, Yuan W, Gao S, Cheng T (2014) Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells. Leukemia 28(5):1071–1080

    PubMed Central  CAS  PubMed  Google Scholar 

  • Luckey CJ, Bhattacharya D, Goldrath AW, Weissman IL, Benoist C, Mathis D (2006) Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci USA 103(9):3304–3309

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ma SK, Chan GC, Wan TS, Lam CK, Ha SY, Lau YL, Chan LC (1998) Near-haploid common acute lymphoblastic leukaemia of childhood with a second hyperdiploid line: a DNA ploidy and fluorescence in-situ hybridization study. Br J Haematol 103(3):750–755

    CAS  PubMed  Google Scholar 

  • Majeti R (2011) Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene 30(9):1009–1019

    CAS  PubMed  Google Scholar 

  • Majeti R, Becker MW, Tian Q, Lee TL, Yan X, Liu R, Chiang JH, Hood L, Clarke MF, Weissman IL (2009) Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. Proc Natl Acad Sci USA 106(9):3396–3401

    PubMed Central  CAS  PubMed  Google Scholar 

  • Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ (2004) Characterization of clonogenic multiple myeloma cells. Blood 103(6):2332–2336

    PubMed Central  CAS  PubMed  Google Scholar 

  • Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, Watkins DN, Huff CA, Jones RJ (2008) Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 68(1):190–197

    PubMed Central  CAS  PubMed  Google Scholar 

  • Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371(16):1507–1517

    PubMed Central  CAS  PubMed  Google Scholar 

  • McKenzie JL, Gan OI, Doedens M, Dick JE (2005) Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood 106(4):1259–1261

    CAS  PubMed  Google Scholar 

  • Miller PG, Al-Shahrour F, Hartwell KA, Chu LP, Jaras M, Puram RV, Puissant A, Callahan KP, Ashton J, McConkey ME, Poveromo LP, Cowley GS, Kharas MG, Labelle M, Shterental S, Fujisaki J, Silberstein L, Alexe G, Al-Hajj MA, Shelton CA, Armstrong SA, Root DE, Scadden DT, Hynes RO, Mukherjee S, Stegmaier K, Jordan CT, Ebert BL (2013) In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 24(1):45–58

    PubMed Central  CAS  PubMed  Google Scholar 

  • Miyamoto T, Weissman IL, Akashi K (2000) AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 97(13):7521–7526

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C, Figueroa ME, Vasanthakumar A, Patel J, Zhao X, Perna F, Pandey S, Madzo J, Song C, Dai Q, He C, Ibrahim S, Beran M, Zavadil J, Nimer SD, Melnick A, Godley LA, Aifantis I, Levine RL (2011) Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20(1):11–24

    PubMed Central  CAS  PubMed  Google Scholar 

  • Moreau P, Voillat L, Benboukher L, Mathiot C, Dumontet C, Robillard N, Herault O, Garnache F, Garand R, Varoqueaux N, Avet-Loiseau H, Harousseau JL, Bataille R, IFM group (2007) Rituximab in CD20 positive multiple myeloma. Leukemia 21(4):835–836

    CAS  PubMed  Google Scholar 

  • Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, Ishii N (2012) Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice. PLoS One 7(6), e37892

    PubMed Central  CAS  PubMed  Google Scholar 

  • Morrison SJ, Weissman IL (1994) The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1(8):661–673

    CAS  PubMed  Google Scholar 

  • Muguruma Y, Matsushita H, Yahata T, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K (2011) Establishment of a xenograft model of human myelodysplastic syndromes. Haematologica 96(4):543–551

    PubMed Central  PubMed  Google Scholar 

  • Nilsson L, Astrand-Grundstrom I, Arvidsson I, Jacobsson B, Hellstrom-Lindberg E, Hast R, Jacobsen SE (2000) Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level. Blood 96(6):2012–2021

    CAS  PubMed  Google Scholar 

  • Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D, Kjeldsen L, Johansson B, Hellstrom-Lindberg E, Hast R, Jacobsen SE (2002) Involvement and functional impairment of the CD34(+)CD38(−)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 100(1):259–267

    CAS  PubMed  Google Scholar 

  • Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE (2011) Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 333(6039):218–221

    CAS  PubMed  Google Scholar 

  • Nowell PC, Hungerford DA (1960) Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 25:85–109

    CAS  PubMed  Google Scholar 

  • Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN, Matsui W (2007) Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 104(10):4048–4053

    PubMed Central  CAS  PubMed  Google Scholar 

  • Pei S, Jordan CT (2012) How close are we to targeting the leukemia stem cell? Best Pract Res Clin Haematol 25(4):415–418

    CAS  PubMed  Google Scholar 

  • Pei S, Minhajuddin M, Callahan KP, Balys M, Ashton JM, Neering SJ, Lagadinou ED, Corbett C, Ye H, Liesveld JL, O’Dwyer KM, Li Z, Shi L, Greninger P, Settleman J, Benes C, Hagen FK, Munger J, Crooks PA, Becker MW, Jordan CT (2013) Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells. J Biol Chem 288(47):33542–33558

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT (2010) Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 464(7290):852–857

    PubMed Central  CAS  PubMed  Google Scholar 

  • Raskind WH, Tirumali N, Jacobson R, Singer J, Fialkow PJ (1984) Evidence for a multistep pathogenesis of a myelodysplastic syndrome. Blood 63(6):1318–1323

    CAS  PubMed  Google Scholar 

  • Rau R, Magoon D, Greenblatt S, Li L, Annesley C, Duffield AS, Huso D, McIntyre E, Clohessy JG, Reschke M, Pandolfi PP, Small D, Brown P (2014) NPMc + cooperates with Flt3/ITD mutations to cause acute leukemia recapitulating human disease. Exp Hematol 42(2):101–113e105

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rieger MA, Schroeder T (2012) Hematopoiesis. Cold Spring Harb Perspect Biol 4(12):a008250

    PubMed Central  PubMed  Google Scholar 

  • Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Honemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21(11):2122–2129

    PubMed Central  CAS  PubMed  Google Scholar 

  • Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O, Blanchet O, Marit G, Gluckman E, Reiffers J, Gardembas M, Mahon FX (2007) Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 109(1):58–60

    CAS  PubMed  Google Scholar 

  • Rowley JD (1973) Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and giemsa staining. Nature 243(5405):290–293

    CAS  PubMed  Google Scholar 

  • Sarry JE, Murphy K, Perry R, Sanchez PV, Secreto A, Keefer C, Swider CR, Strzelecki AC, Cavelier C, Recher C, Mansat-De Mas V, Delabesse E, Danet-Desnoyers G, Carroll M (2011) Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rgammac-deficient mice. J Clin Invest 121(1):384–395

    PubMed Central  CAS  PubMed  Google Scholar 

  • Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJ, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ, Brown AM, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JC, Dick JE, Consortium HP-LGP (2014) Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506(7488):328–333

    CAS  PubMed  Google Scholar 

  • Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, Kotb M, Gillies SD, King M, Mangada J, Greiner DL, Handgretinger R (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174(10):6477–6489

    CAS  PubMed  Google Scholar 

  • Taussig DC, Pearce DJ, Simpson C, Rohatiner AZ, Lister TA, Kelly G, Luongo JL, Danet-Desnoyers GA, Bonnet D (2005) Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood 106(13):4086–4092

    PubMed Central  CAS  PubMed  Google Scholar 

  • Taussig DC, Miraki-Moud F, Anjos-Afonso F, Pearce DJ, Allen K, Ridler C, Lillington D, Oakervee H, Cavenagh J, Agrawal SG, Lister TA, Gribben JG, Bonnet D (2008) Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood 112(3):568–575

    CAS  PubMed  Google Scholar 

  • Taussig DC, Vargaftig J, Miraki-Moud F, Griessinger E, Sharrock K, Luke T, Lillington D, Oakervee H, Cavenagh J, Agrawal SG, Lister TA, Gribben JG, Bonnet D (2010) Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(−) fraction. Blood 115(10):1976–1984

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, Astrand-Grundstrom I, Strombeck B, Horvat A, Ferry H, Dhanda RS, Hast R, Ryden T, Vyas P, Gohring G, Schlegelberger B, Johansson B, Hellstrom-Lindberg E, List A, Nilsson L, Jacobsen SE (2010) Persistent malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med 363(11):1025–1037

    CAS  PubMed  Google Scholar 

  • Teitell MA, Pandolfi PP (2009) Molecular genetics of acute lymphoblastic leukemia. Annu Rev Pathol 4:175–198

    CAS  PubMed  Google Scholar 

  • Uchida N, Dykstra B, Lyons KJ, Leung FY, Eaves CJ (2003) Different in vivo repopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics. Exp Hematol 31(12):1338–1347

    CAS  PubMed  Google Scholar 

  • Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA (2010) The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 327(5973):1650–1653

    PubMed Central  CAS  PubMed  Google Scholar 

  • Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM (2009) A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 113(22):5418–5422

    PubMed Central  CAS  PubMed  Google Scholar 

  • Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, Wartman LD, Lamprecht TL, Liu F, Xia J, Kandoth C, Fulton RS, McLellan MD, Dooling DJ, Wallis JW, Chen K, Harris CC, Schmidt HK, Kalicki-Veizer JM, Lu C, Zhang Q, Lin L, O’Laughlin MD, McMichael JF, Delehaunty KD, Fulton LA, Magrini VJ, McGrath SD, Demeter RT, Vickery TL, Hundal J, Cook LL, Swift GW, Reed JP, Alldredge PA, Wylie TN, Walker JR, Watson MA, Heath SE, Shannon WD, Varghese N, Nagarajan R, Payton JE, Baty JD, Kulkarni S, Klco JM, Tomasson MH, Westervelt P, Walter MJ, Graubert TA, DiPersio JF, Ding L, Mardis ER, Wilson RK (2012) The origin and evolution of mutations in acute myeloid leukemia. Cell 150(2):264–278

    PubMed Central  CAS  PubMed  Google Scholar 

  • Will B, Zhou L, Vogler TO, Ben-Neriah S, Schinke C, Tamari R, Yu Y, Bhagat TD, Bhattacharyya S, Barreyro L, Heuck C, Mo Y, Parekh S, McMahon C, Pellagatti A, Boultwood J, Montagna C, Silverman L, Maciejewski J, Greally JM, Ye BH, List AF, Steidl C, Steidl U, Verma A (2012) Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations. Blood 120(10):2076–2086

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wright JJ, Poplack DG, Bakhshi A, Reaman G, Cole D, Jensen JP, Korsmeyer SJ (1987) Gene rearrangements as markers of clonal variation and minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 5(5):735–741

    CAS  PubMed  Google Scholar 

  • Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, McMichael JF, Schmidt HK, Yellapantula V, Miller CA, Ozenberger BA, Welch JS, Link DC, Walter MJ, Mardis ER, Dipersio JF, Chen F, Wilson RK, Ley TJ, Ding L (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 20(12):1472–1478

    PubMed Central  CAS  PubMed  Google Scholar 

  • Yaccoby S, Barlogie B, Epstein J (1998) Primary myeloma cells growing in SCID-hu mice: a model for studying the biology and treatment of myeloma and its manifestations. Blood 92(8):2908–2913

    CAS  PubMed  Google Scholar 

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  1. James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Michael W. Becker & Kristen M. O’Dwyer

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  1. Faculty of Biol. Scs. Dept. of Mol. Gen., Tarbiat Modares University , Tehran, Iran

    Sadegh Babashah

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Becker, M.W., O’Dwyer, K.M. (2015). Leukemic and Lymphoid Stem Cells. In: Babashah, S. (eds) Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-21030-8_13

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