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Early Hematopoietic Differentiation in Acute Lymphoblastic Leukemia: The Interplay Between Leukemia-Initiating Cells and Abnormal Bone Marrow Microenvironment

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Etiology of Acute Leukemias in Children

Abstract

By virtue of their self-renewal and tightly regulated multi-lineage differentiation properties, hematopoietic stem cells (HSCs) generate the whole blood system throughout postnatal life. During malignant hematological disorders, including acute leukemias, a number of intrinsic and extrinsic cues influence the hematopoietic differentiation pathway and cooperate to make aberrant cell fate decisions concomitant with cell transformation. The cellular origin of these disorders is a fundamental matter in question. In keeping with the hierarchical model of tumor evolution, a conspicuous and unique leukemic stem cell (LSC) population is most likely the foundation of acute and chronic myeloid leukemias. In contrast, all B-cell differentiation stages in acute lymphoblastic leukemia (ALL) function as leukemia-initiating cells (LICs), are endowed with primitive stem cell properties and are apparently responsible for the long-term maintenance of tumor growth within the bone marrow (BM) and for relapse of the disease following remission. Furthermore, LICs reveal the ability to create irregular BM microenvironments that may result in proinflammatory scenarios with a permissive role by allowing leukemic cell development at the expense of normal hematopoiesis. This chapter outlines the recent findings contributing to the understanding of malignant hematopoiesis through the biology of early stem and progenitor cells in the context of abnormal microenvironments within leukemic BM. By unraveling the role of leukemic precursor cells in the initiation of local inflammatory processes leading to hematopoietic instability, we may learn about additional mechanisms co-participating in the etiology and maintenance of this pathological condition.

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References

  • Abollo-Jiménez F, Campos-Sanches E, Sagrera A, Muñoz ME, Galan AI, Jimenez R, Cobaleda C. The dark side of cellular plasticity: stem cells in development and cancer. In: Shostak S. editor. Cancer Stem Cells Theories and Practice. Rijeka, Croatia: InTech; 2011. ISBN: 978-953-307-225-8.

    Google Scholar 

  • Abraham S, Hopcroft L, Bhatia R, Koschmieder S, Whetton A, Holyoake T. Models to study chronic myeloid leukemia cancer stem cells. In: Rajasekhar V. editor. Cancer stem cells.Hoboken, New Jersey: John Wiley & Sons, Inc; 2014.

    Google Scholar 

  • Ailles LE, Weissman IL. Cancer stem cells in solid tumors. Curr Opin Biotechnol. 2007;18:460–6.

    Article  CAS  PubMed  Google Scholar 

  • Armstrong F, Brunet de la Grange P, Gerby B, Rouyez MC, Calvo J, Fontenay M, Boissel N, Dombret H, Baruchel A, Landman-Parker J, Roméo PH, Ballerini P, Pflumio F. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity. Blood. 2009;113(8):1730–40.

    Google Scholar 

  • Baccelli I, Trumpp A. The evolving concept of cancer and metastasis stem cells. J Cell Biol. 2012;198:281–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bell JJ, Bhandoola A. The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature. 2008;452:764–7.

    Article  CAS  PubMed  Google Scholar 

  • Benz C, Copley MR, Kent DG, Wohrer S, Cortes A, Aghaeepour N, Ma E, Mader H, Rowe K, Day C, Treloar D, Brinkman RR, Eaves CJ. Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs. Cell Stem Cell. 2012;10:273–83.

    Article  CAS  PubMed  Google Scholar 

  • Bhandoola A, Sambandam A. From stem cell to T cell: one route or many? Nat Rev Immunol. 2006;6:117–26.

    Article  CAS  PubMed  Google Scholar 

  • Bhatla T, Jones CL, Meyer JA, Vitanza NA, Raetz EA, Carroll WL. The biology of relapsed acute lymphoblastic leukemia: opportunities for therapeutic interventions. J Pediatr Hematol Oncol. 2014;36:413–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bigildeev AE, Shipounova IN, Svinareva DA, Drize NJ. Leukemia cells invading the liver express liver chemokine receptors and possess characteristics of leukemia stem cells in mice with MPD-like myeloid leukemia. Exp Hematol. 2011;39:187–94.

    Article  CAS  PubMed  Google Scholar 

  • Blom B, Spits H. Development of human lymphoid cells. Annu Rev Immunol. 2006;24:287–320.

    Article  CAS  PubMed  Google Scholar 

  • Bomken S, Fiser K, Heidenreich O, Vormoor J. Understanding the cancer stem cell. Br J Cancer. 2010;103(4):439–45.

    Google Scholar 

  • Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.

    Article  CAS  PubMed  Google Scholar 

  • Boos MD, Yokota Y, Eberl G, Kee BL. Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J Exp Med. 2007;204:1119–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campos-Sanchez E, Toboso-Navasa A, Romero-Camarero I, Barajas-Diego M, Sanchez-Garcia I, Cobaleda C. Acute lymphoblastic leukemia and developmental biology: a crucial interrelationship. Cell Cycle. 2011;10:3473–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chavez-Gonzalez A, Aviles-Vazquez S, Moreno-Lorenzana D, Mayani H. Hematopoietic stem cells in chronic myeloid leukemia. In: Alimoghaddam K editor. Stem cell biology in normal life and diseases. Rijeka, Croatia: InTech; 2013.

    Google Scholar 

  • Chavez-Gonzalez A, Dorantes-Acosta E, Moreno-Lorenzana D, Alvarado-Moreno A, Arriaga-Pizano L, Mayani H. Expression of CD90, CD96, CD117, and CD123 on different hematopoietic cell populations from pediatric patients with acute myeloid leukemia. Arch Med Res. 2014;45:343–50.

    Article  CAS  PubMed  Google Scholar 

  • Chung SS, Park CY. Acute myeloid leukemia cells-updates and controversies. In: Rajasekhar V. editor. Cancer stem cells. Hoboken, New Jersey: John Wiley & Sons, Inc, Wiley-Blackwell; 2014.

    Google Scholar 

  • Cobaleda C, Gutiérrez-Cianca N, Pérez-Losada J, Flores T, García-Sanz R, González M, Sánchez-García I. A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Blood. 2000;95(3):1007–13.

    Google Scholar 

  • Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008;322:1861–5.

    Article  CAS  PubMed  Google Scholar 

  • Conforti A, Biagini S, DEL Bufalo F, Sirleto P, Angioni A, Starc N, Li Pira G, Moretta F, Proia A, Contoli B, Genovese S, Ciardi C, Avanzini MA, Rosti V, Lo-Coco F, Locatelli F, Bernardo ME. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. PLoS ONE. 2013;8:e76989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corre J, Mahtouk K, Attal M, Gadelorge M, Huynh A, Fleury-Cappellesso S, Danho C, Laharrague P, Klein B, Reme T, Bourin P. Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. Leukemia. 2007;21:1079–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cox CV, Evely RS, Oakhill A, Pamphilon DH, Goulden NJ, Blair A. Characterization of acute lymphoblastic leukemia progenitor cells. Blood. 2004;104:2919–25.

    Article  CAS  PubMed  Google Scholar 

  • Cox CV, Martin HM, Kearns PR, Virgo P, Evely RS, Blair A. Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood. 2007;109:674–82.

    Article  CAS  PubMed  Google Scholar 

  • Cox CV, Diamanti P, Evely RS, Kearns PR, Blair A. Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood. 2009;113:3287–96.

    Article  CAS  PubMed  Google Scholar 

  • Deng CH, Zhang QP. Leukemia stem cells in drug resistance and metastasis. Chin Med J (Engl). 2010;123:954–60.

    Google Scholar 

  • Diamanti P, Cox CV, Moppett JP, Blair A. Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia. Blood. 2013;121:1384–93.

    Article  CAS  PubMed  Google Scholar 

  • Dias S, Hattori K, Zhu Z, Heissig B, Choy M, Lane W, Wu Y, Chadburn A, Hyjek E, Gill M, Hicklin DJ, Witte L, Moore MA, Rafii S. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest. 2000;106:511–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dick JE. Stem cell concepts renew cancer research. Blood. 2008;112:4793–807.

    Article  CAS  PubMed  Google Scholar 

  • Dorantes-Acosta E, Pelayo R. Lineage switching in acute leukemias: a consequence of stem cell plasticity? Bone Marrow Res. 2012;2012:406796.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dorantes-Acosta E, Chavez-Gonzalez A, Santos JI, Medina-Sanson A, Mayani H. Defective in vitro growth of primitive hematopoietic cells from pediatric patients with acute myeloid leukemia. Pediatr Blood Cancer. 2008;51:741–6.

    Article  PubMed  Google Scholar 

  • Dorantes-Acosta E, Vadillo E, Contreras-Quiroz A, Balandran JC, Arriaga-Pizano L, Purizaca J, Huerta-Yepez S, Jimenez E, Aguilera W, Medina-Sanson A, Mayani H, Pelayo R. TLR stimulation of bone marrow lymphoid precursors from childhood acute leukemia modifies their differentiation potentials. Biomed Res Int. 2013;2013:846724.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE. Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat Immunol. 2010;11:585–93.

    Article  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. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med. 2011;17:1086–93.

    Article  CAS  PubMed  Google Scholar 

  • Espinoza-Hernandez L, Cruz-Rico J, Benitez-Aranda H, Martinez-Jaramillo G, Rodriguez-Zepeda MC, Velez-Ruelas MA, Mayani H. In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia. Leuk Res. 2001;25:295–303.

    Article  CAS  PubMed  Google Scholar 

  • Feng S, Cen J, Huang Y, Shen H, Yao L, Wang Y, Chen Z. Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins. PLoS ONE. 2011;6:e20599.

    Article  CAS  PubMed  PubMed Central  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. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011;19:138–52.

    Article  CAS  PubMed  Google Scholar 

  • Greaves MF, Wiemels J. Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer. 2003;3:639–49.

    Article  CAS  PubMed  Google Scholar 

  • Greve B, Kelsch R, Spaniol K, Eich HT, Gotte M. Flow cytometry in cancer stem cell analysis and separation. Cytom A. 2012;81:284–93.

    Article  Google Scholar 

  • Gu TL, Nardone J, Wang Y, Loriaux M, Villen J, Beausoleil S, Tucker M, Kornhauser J, Ren J, Macneill J, Gygi SP, Druker BJ, Heinrich MC, Rush J, Polakiewicz RD. Survey of activated FLT3 signaling in leukemia. PLoS ONE. 2011;6:e19169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta S, Rivera-Luna R, Ribeiro RC, Howard SC. Pediatric oncology as the next global child health priority: the need for national childhood cancer strategies in low- and middle-income countries. PLoS Med. 2014;11:e1001656.

    Article  PubMed  PubMed Central  Google Scholar 

  • Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, Jordan CT. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98:2301–7.

    Article  CAS  PubMed  Google Scholar 

  • Hogan LE, Meyer JA, Yang J, Wang J, Wong N, Yang W, Condos G, Hunger SP, Raetz E, Saffery R, Relling MV, Bhojwani D, Morrison DJ, Carroll WL. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood. 2011;118:5218–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holyoake T, Jiang X, Eaves C, Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94:2056–64.

    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. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25(11):1315–21.

    Google Scholar 

  • Iwasaki H, Akashi K. Myeloid lineage commitment from the hematopoietic stem cell. Immunity. 2007;26:726–40.

    Article  CAS  PubMed  Google Scholar 

  • Izraeli S. Application of genomics for risk stratification of childhood acute lymphoblastic leukaemia: from bench to bedside? Br J Haematol. 2010;151:119–31.

    Article  CAS  PubMed  Google Scholar 

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

    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. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia. 2000;14:1777–84.

    Article  CAS  PubMed  Google Scholar 

  • Juarez-Velazquez R, Reyes-Leon A, Salas-Labadia C, Rivera-Luna R, Velasco-Hidalgo L, Lopez-Hernandez G, Lopez-Santiago N, Paredes-Aguilera R, Dominguez-Lopez A, Bernaldez R, Perez-Vera P. Significance of CASP8AP2 and H2AFZ expression in survival and risk of relapse in children with acute lymphoblastic leukemia. Leuk Lymphoma. 2014;55:2305–11.

    Article  CAS  PubMed  Google Scholar 

  • Kakarala M, Wicha MS. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 2008;26:2813–20.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawamata N, Pennella MA, Woo JL, Berk AJ, Koeffler HP. Dominant-negative mechanism of leukemogenic PAX5 fusions. Oncogene. 2012;31:966–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21.

    Article  CAS  PubMed  Google Scholar 

  • Kinlen LJ. Epidemiological evidence for an infective basis in childhood leukaemia. Br J Cancer. 1995;71:1–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohn LA, Hao QL, Sasidharan R, Parekh C, Ge S, Zhu Y, Mikkola HK, Crooks GM. Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin. Nat Immunol. 2012;13:963–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell. 1997;91:661–72.

    Article  CAS  PubMed  Google Scholar 

  • Kong Y, Yoshida S, Saito Y, Doi T, Nagatoshi Y, Fukata M, Saito N, Yang SM, Iwamoto C, Okamura J, Liu KY, Huang XJ, Lu DP, Shultz LD, Harada M, Ishikawa F. CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL. Leukemia. 2008;22:1207–13.

    Article  CAS  PubMed  Google Scholar 

  • Krause DS, VAN Etten RA. Right on target: eradicating leukemic stem cells. Trends Mol Med. 2007;13:470–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krawczyc J, O’Dwyer M, Swords R, Freeman C, Giles FJ. The role of inflammation in leukemia. In: Agarwal BB et al. editors. Inflammation and Cancer, Advances in Experimental Medicine and biology. Basel: Springer; 2014.

    Google Scholar 

  • Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells. 2005;23:879–94.

    Article  CAS  PubMed  Google Scholar 

  • Lane SW, Wang YJ, Lo Celso C, Ragu C, Bullinger L, Sykes SM, Ferraro F, Shterental S, Lin CP, Gilliland DG, Scadden DT, Armstrong SA, Williams DA. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011;118:2849–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.

    Article  CAS  PubMed  Google Scholar 

  • Le Viseur C, Hotfilder M, Bomken S, Wilson K, Rottgers S, Schrauder A, Rosemann A, Irving J, Stam RW, Shultz LD, Harbott J, Jurgens H, Schrappe M, Pieters R, Vormoor J. In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties. Cancer Cell. 2008;14:47–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lemoli RM, Salvestrini V, Bianchi E, Bertolini F, Fogli M, Amabile M, Tafuri A, Salati S, Zini R, Testoni N, Rabascio C, Rossi L, Martin-Padura I, Castagnetti F, Marighetti P, Martinelli G, Baccarani M, Ferrari S, Manfredini R. Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib. Blood. 2009;114:5191–200.

    Article  CAS  PubMed  Google Scholar 

  • Lilljebjorn H, Rissler M, Lassen C, Heldrup J, Behrendtz M, Mitelman F, Johansson B, Fioretos T. Whole-exome sequencing of pediatric acute lymphoblastic leukemia. Leukemia. 2012;26:1602–7.

    Article  CAS  PubMed  Google Scholar 

  • Lippitz BE. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14:e218–28.

    Article  CAS  PubMed  Google Scholar 

  • Magrath I, Steliarova-Foucher E, Epelman S, Ribeiro RC, Harif M, Li CK, Kebudi R, Macfarlane SD, Howard SC. Paediatric cancer in low-income and middle-income countries. Lancet Oncol. 2013;14:e104–16.

    Article  PubMed  Google Scholar 

  • Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2):286–99.

    Google Scholar 

  • Male V, Nisoli I, Kostrzewski T, Allan DS, Carlyle JR, Lord GM, Wack A, Brady HJ. The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression. J Exp Med. 2014;211:635–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.

    Article  CAS  PubMed  Google Scholar 

  • Manz MG, Miyamoto T, Akashi K, Weissman IL. Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci U S A. 2002;99:11872–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Massberg S, Schaerli P, Knezevic-Maramica I, Kollnberger M, Tubo N, Moseman EA, Huff IV, Junt T, Wagers AJ, Mazo IB, VON Andrian UH. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell. 2007;131:994–1008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maude SL, Tasian SK, Vincent T, Hall JW, Sheen C, Roberts KG, Seif AE, Barrett DM, Chen IM, Collins JR, Mullighan CG, Hunger SP, Harvey RC, Willman CL, Fridman JS, Loh ML, Grupp SA, Teachey DT. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2012;120(17):3510–8.

    Google Scholar 

  • Mayani H, Flores-Figueroa E, Chávez-González A. In vitro biology of human myeloid leukemia. Leuk Res. 2009;33(5):624–37.

    Google Scholar 

  • Mazo IB, Massberg S, Von Andrian UH. Hematopoietic stem and progenitor cell trafficking. Trends Immunol. 2011;32:493–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McManus S, Ebert A, Salvagiotto G, Medvedovic J, Sun Q, Tamir I, Jaritz M, Tagoh H, Busslinger M. The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells. EMBO J. 2011;30:2388–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mcneil DE, Cote TR, Clegg L, Mauer A. SEER update of incidence and trends in pediatric malignancies: acute lymphoblastic leukemia. Med Pediatr Oncol. 2002;39:554–7; discussion 552–3.

    Article  PubMed  Google Scholar 

  • Meijerink JP, DEN Boer ML, Pieters R. New genetic abnormalities and treatment response in acute lymphoblastic leukemia. Semin Hematol. 2009;46:16–23.

    Article  PubMed  Google Scholar 

  • Merchand-Reyes G, Pelayo R, Pavon L, Pestell R, Velasco-Velázquez M. Role of cancer stem cells in metastasis. In: Rajasekhar V. editor. Cancer stem cells. Hoboken, New Jersey: John Wiley & Sons, Inc; 2014.

    Google Scholar 

  • Mjosberg J, Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, Te Velde AA, Fokkens WJ, Van Drunen CM, Spits H. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity. 2012;37:649–59.

    Article  PubMed  CAS  Google Scholar 

  • Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen IM, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP, Willman CL. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2009;106(23):9414–8.

    Google Scholar 

  • Mullighan CG. The molecular genetic makeup of acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Prog. 2012;2012:389–96.

    Google Scholar 

  • Mullighan CG, Willman CL. Advances in the biology of acute lymphoblastic leukemia-from genomics to the clinic. J Adolesc Young Adult Oncol. 2011;1:77–86.

    Article  PubMed  PubMed Central  Google Scholar 

  • Naik SH, Perie L, Swart E, Gerlach C, Van Rooij N, De Boer RJ, Schumacher TN. Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature. 2013;496:229–32.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12:133–43.

    CAS  PubMed  Google Scholar 

  • Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science. 2011a;333:218–21.

    Article  CAS  PubMed  Google Scholar 

  • Notta F, Mullighan CG, Wang JC, Poeppl A, Doulatov S, Phillips LA, Ma J, Minden MD, Downing JR, Dick JE. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature. 2011b;469:362–7.

    Article  CAS  PubMed  Google Scholar 

  • Nutt SL, Heavey B, Rolink AG, Busslinger M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature. 1999;401:556–62.

    Article  CAS  PubMed  Google Scholar 

  • Oguro H, Ding L, Morrison SJ. SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. Cell Stem Cell. 2013;13:102–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orkin SH, Pera M. Stem cells down under-ISSCR 2007. Cell Stem Cell. 2007;1:271–6.

    Article  CAS  PubMed  Google Scholar 

  • Pelayo R, Miyazaki K, Huang J, Garrett KP, Osmond DG, Kincade PW. Cell cycle quiescence of early lymphoid progenitors in adult bone marrow. Stem Cells. 2006;24:2703–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pelayo R, Dorantes-Acosta E, Vadillo E, Fuentes-Panana EM. From HSC to B-lymphoid cells in normal and malignant hematopoiesis. In: Pelayo R. editor. Advances in hematopoietic stem cell research. Rijeka, Croatia: InTech; 2012.

    Google Scholar 

  • Perez-Saldivar ML, Fajardo-Gutierrez A, Bernaldez-Rios R, Martinez-Avalos A, Medina-Sanson A, Espinosa-Hernandez L, Flores-Chapa JDED, Amador-Sanchez R, Penaloza-Gonzalez JG, Alvarez-Rodriguez FJ, Bolea-Murga V, Flores-Lujano J, Rodriguez-Zepeda MDELC, Rivera-Luna R, Dorantes-Acosta EM, Jimenez-Hernandez E, Alvarado-Ibarra M, Velazquez-Avina MM, Torres-Nava JR, Duarte-Rodriguez DA, Paredes-Aguilera R, Del Campo-Martinez MDEL, Cardenas-Cardos R, Alamilla-Galicia PH, Bekker-Mendez VC, Ortega-Alvarez MC, Mejia-Arangure JM. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology. BMC Cancer. 2011;11:355.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50:185–96.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pui CH, Rubnitz JE, Hancock ML, Downing JR, Raimondi SC, Rivera GK, Sandlund JT, Ribeiro RC, Head DR, Relling MV, Evans WE, Behm FG. Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. J Clin Oncol. 1998;16:3768–73.

    CAS  PubMed  Google Scholar 

  • Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.

    Article  CAS  PubMed  Google Scholar 

  • Purizaca J, Meza I, Pelayo R. Early lymphoid development and microenvironmental cues in B-cell acute lymphoblastic leukemia. Arch Med Res. 2012;43:89–101.

    Article  PubMed  Google Scholar 

  • Purizaca J, Contreras-Quiroz A, Dorantes-Acosta E, Vadillo E, Arriaga-Pizano L, Fuentes-Figueroa S, Villagomez-Barragan H, Flores-Guzman P, Alvarado-Moreno A, Mayani H, Meza I, Hernandez R, Huerta-Yepez S, Pelayo R. Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1. Clin Dev Immunol. 2013;2013:349067.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Raaijmakers MH. Niche contributions to oncogenesis: emerging concepts and implications for the hematopoietic system. Haematologica. 2011;96:1041–8.

    Article  PubMed  PubMed Central  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. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raff T, Bruggermann M. Leukemia-initiating cells in acute lymphoblastic leukemia. In: Rajasekhar V. editor. Cancer stem cells. Hoboken, New Jersey: John Wiley & Sons, Inc, Wiley-Blackwell; 2014.

    Google Scholar 

  • Rajendran P, Dalerba P. Theoretical and experimental foundations of the “Cancer stem cell” model. In: Rajashekhar V, editor. Cancer stem cells. Hoboken, New Jersey: John Wiley & Sons, Inc; 2014.

    Google Scholar 

  • Rehe K, Wilson K, Bomken S, Williamson D, Irving J, DEN Boer ML, Stanulla M, Schrappe M, Hall AG, Heidenreich O, Vormoor J. Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations. EMBO Mol Med. 2013;5:38–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, Behm FG, Campana D, Razzouk BI, Ribeiro RC, Downing JR, Pui CH. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood. 2009;113:5083–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serafini N, Klein Wolterink RG, Satoh-Takayama N, Xu W, Vosshenrich CA, Hendriks RW, Di Santo JP. Gata3 drives development of RORgammat+ group 3 innate lymphoid cells. J Exp Med. 2014;211:199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah DK, Zuniga-Pflucker JC. An overview of the intrathymic intricacies of T cell development. J Immunol. 2014;192:4017–23.

    Article  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, Consortium HP-LGP, Brown AM, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JC, Dick JE. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506:328–33.

    Article  CAS  PubMed  Google Scholar 

  • Shortman K, Sathe P, Vremec D, Naik S, O’Keeffe M. Plasmacytoid dendritic cell development. Adv Immunol. 2013;120:105–26.

    Article  CAS  PubMed  Google Scholar 

  • Sipkins DA, Wei X, Wu JW, Runnels JM, Cote D, Means TK, Luster AD, Scadden DT, Lin CP. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435:969–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241:58–62.

    Article  CAS  PubMed  Google Scholar 

  • Spits H, Cupedo T. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol. 2012;30:647–75.

    Article  CAS  PubMed  Google Scholar 

  • Sultana DA, Zhang SL, Todd SP, Bhandoola A. Expression of functional P-selectin glycoprotein ligand 1 on hematopoietic progenitors is developmentally regulated. J Immunol. 2012;188:4385–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi S. Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications. J Hematol Oncol. 2011;4:13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan BT, Park CY, Ailles LE, Weissman IL. The cancer stem cell hypothesis: a work in progress. Lab Invest. 2006;86:1203–7.

    Article  CAS  PubMed  Google Scholar 

  • Tavor S, Petit I, Porozov S, Avigdor A, Dar A, Leider-Trejo L, Shemtov N, Deutsch V, Naparstek E, Nagler A, Lapidot T. CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res. 2004;64:2817–24.

    Article  CAS  PubMed  Google Scholar 

  • Terwijn M, Zeijlemaker W, Kelder A, Rutten AP, Snel AN, Scholten WJ, Pabst T, Verhoef G, Lowenberg B, Zweegman S, Ossenkoppele GJ, Schuurhuis GJ. Leukemic stem cell frequency: a strong biomarker for clinical outcome in acute myeloid leukemia. PLoS ONE. 2014;9:e107587.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vadillo E, Pelayo R. El sistema hematopoyético a partir de células troncales. In: Pelayo R, editor. Células Troncales y Medicina Regenerativa. Mexico: PUIS; 2011.

    Google Scholar 

  • Vadillo E, Pelayo R. Toll-like receptors in development and function of the hematopoietic system. Rev Invest Clin. 2012;64:461–76.

    CAS  PubMed  Google Scholar 

  • Vadillo E, Dorantes-Acosta E, Pelayo R. Regulation of hematopoietic stem/progenitor cells by inflammation cues. In: Perez-Martínez et al (eds). Molecular Aspects of Inflammation Kerala, India: Research Signpost; 2013.

    Google Scholar 

  • Vadillo E, Dorantes-Acosta E, Arriaga-Pizano L, Chavez-Gonzalez A, Reyes-Maldonado E, Garrett KP, Mayani H, Kincade PW, Pelayo R. Adult, but not neonatal, human lymphoid progenitors respond to TLR9 ligation by producing functional NK-like cells. Exp Hematol. 2014;42:562–73, e3.

    Article  CAS  PubMed  Google Scholar 

  • Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.

    Article  CAS  PubMed  Google Scholar 

  • Vicente Lopez A, Vazquez Garcia MN, Melen GJ, Entrena Martinez A, Cubillo Moreno I, Garcia-Castro J, Orellana MR, Gonzalez AG. Mesenchymal stromal cells derived from the bone marrow of acute lymphoblastic leukemia patients show altered BMP4 production: correlations with the course of disease. PLoS ONE. 2014;9:e84496.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vilchis A, Contreras-Quiroz A, Vadillo E, Dorantes-Acosta E, Reyes-Lopez A, Quintela-Nuñez Del Prado H, Venegas-Vazquez J, Mayani H, Ortiz-Navarrete V, Lopez-Martinez B, Pelayo R. Boen marrow cells in acute lymphoblastic leukemia create a pro-inflammatory microenviroment influencing normal hematopoietic differentiation fates. Biomed Res Int. 2015;2015:386165. doi: 10.1155/2015/386165.

    Google Scholar 

  • Vosshenrich CA, Di Santo JP. Developmental programming of natural killer and innate lymphoid cells. Curr Opin Immunol. 2013;25:130–8.

    Article  CAS  PubMed  Google Scholar 

  • Welner RS, Pelayo R, Kincade PW. Evolving views on the genealogy of B cells. Nat Rev Immunol. 2008;8:95–106.

    Article  CAS  PubMed  Google Scholar 

  • Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, Barlow JL, Neill DR, Panova V, Koch U, Radtke F, Hardman CS, Hwang YY, Fallon PG, McKenzie AN. Transcription factor RORalpha is critical for nuocyte development. Nat Immunol. 2012;13:229–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woo JS, Alberti MO, Tirado CA. Childhood B-acute lymphoblastic leukemia: a genetic update. Exp Hematol Oncol. 2014;3:16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie Y, Davies SM, Xiang Y, Robison LL, Ross JA. Trends in leukemia incidence and survival in the United States (1973–1998). Cancer. 2003;97:2229–35.

    Article  PubMed  Google Scholar 

  • Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y, Cheng C, Pei D, Scheet P, Burchard EG, Eng C, Huntsman S, Torgerson DG, Dean M, Winick NJ, Martin PL, Camitta BM, Bowman WP, Willman CL, Carroll WL, Mullighan CG, Bhojwani D, Hunger SP, Pui CH, Evans WE, Relling MV, Loh ML, Yang JJ. Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J Natl Cancer Inst. 2013;105:733–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M, Lu J, Wang X, Cen J, Fan G, Hu S. Early precursor T-lymphoblastic leukaemia/lymphoma arising from paediatric chronic myeloid leukaemia - unusual lymph node blast crisis. Br J Haematol. 2013;161(1):136-9.

    Google Scholar 

  • Zlotoff DA, Sambandam A, Logan TD, Bell JJ, Schwarz BA, Bhandoola A. CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus. Blood. 2010;115:1897–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuna J, Madzo J, Krejci O, Zemanova Z, Kalinova M, Muzikova K, Zapotocky M, Starkova J, Hrusak O, Horak J, Trka J. ETV6/RUNX1 (TEL/AML1) is a frequent prenatal first hit in childhood leukemia. Blood. 2011;117:368–9; author reply 370–1.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Our work is supported by the “Federico Gómez” Children’s Hospital (Grant HIM/018/2013), the National Council of Science and Technology (CONACyT, Grant CB-2010-01-152695), and the Mexican Institute for Social Security (IMSS, Grant FIS/IMSS/PROT/G14/1289). Eduardo Vadillo holds a scholarship from CONACyT.

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Authors and Affiliations

  1. Clinic Laboratory Department, “Federico Gómez” Children’s Hospital, Doctor Márquez 162, Colonia Doctores, 06720, Mexico City, Mexico

    Armando Vilchis-Ordoñez

  2. Hematology and Oncology Department, “Federico Gómez” Children’s Hospital, Doctor Márquez 162, Colonia Doctores, 06720, Mexico City, Mexico

    Elisa Dorantes-Acosta

  3. Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Av. Cuauhtemoc 330, Colonia Doctores, 06720, Mexico City, Mexico

    Eduardo Vadillo & Rosana Pelayo

  4. Central Laboratory Department, “Federico Gómez” Children’s Hospital, Doctor Márquez 162, Colonia Doctores, 06720, Mexico City, Mexico

    Briceida López-Martínez

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  1. Armando Vilchis-Ordoñez
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  2. Elisa Dorantes-Acosta
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  3. Eduardo Vadillo
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  5. Rosana Pelayo
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Correspondence to Rosana Pelayo .

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  1. Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, City, Distrito Federal, Mexico

    Juan Manuel Mejía-Aranguré

Glossary

Cancer stem cell

 A primitive cell capable of generating tumor indefinitely and all the cellular subsets that constitute the malignant mass. Cancer stem cells may have the ability to control the maintenance, propagation, metastasis, and relapse of transformed cells.

Hematopoiesis

 A highly ordered, multi-step differentiation process that starts in a unique population of self-renewing HSCs, which gradually commit to lymphoid or myeloid lineage fates until the formation of mature blood cells.

Hematopoietic microenviroment

 A specialized structure consisting of a complex network of mesenchymal cells, osteoblasts, endothelial cells, fibroblasts, adipocytes, innate and adaptive immune cells, and their products, including extracellular matrix, cytokines, chemokines, and growth factors. It is essential for supporting HSC differentiation throughout life.

Leukemia-initiating cell

 Cancer-initiating cells with either progenitor or differentiating cell phenotypes, capable of recapitulating leukemia in serial transplantation mouse models. LICs are endowed with some stemness and plasticity properties.

Plasticity

 An essential feature of developing tissues that refers to the capacity of cells to adopt biological properties of other cell types. Multi-lineage potential, dedifferentiation, transdifferentiation, and reprogramming are all manifestations of plasticity.

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Vilchis-Ordoñez, A., Dorantes-Acosta, E., Vadillo, E., López-Martínez, B., Pelayo, R. (2016). Early Hematopoietic Differentiation in Acute Lymphoblastic Leukemia: The Interplay Between Leukemia-Initiating Cells and Abnormal Bone Marrow Microenvironment. In: Mejía-Aranguré, J. (eds) Etiology of Acute Leukemias in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-05798-9_9

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