Abstract
Classifying the hematological malignancies by assigning cells to their normal counterpart and describing the nature of disease progression are entirely reliant on an accurate picture for the development of the multifarious types of blood and immune cells. In recent years, our understanding of the complex relationships between the various hematopoietic stem cell-derived cell lineages has undergone substantial revision. There has been similar progress in how we describe the nature of the “target” cells that genetic insults transform to give rise to the hematological malignancies. Here I describe how both longstanding and new information has influenced classifying, for diagnosis, the hematological malignancies.
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References
Kuppers R, Schwering I, Braininger A et al (2002) Biology of Hodgkin’s lymphoma, Ann Oncol. 13(Suppl 1):11
Brown G, Hogg N, Greaves MF (1975) A candidate leukemia-specific antigen. Nature 258:454–456
Brown G, Capellaro D, Greaves MF (1975) Leukemia-associated antigens in man. JNCI 55:1281–1289
Greaves MF, Brown G, Haywood A (1976) A panel of markers for human lymphocyte subpopulations. Applications to disease. In: Beers RF Jnr, Basset E (eds) The role of immunological factors in infectious, allergic and autoimmune processes. Raven Press, New York
Brown G, Greaves MF, Lister TA, Rapson N et al (1974) The expression of human T and B lymphocyte cell surface markers on leukemia cells. Lancet 7883:753–755
Greaves MF, Brown G, Capellaro D et al (1976) Immunological approaches to the identification of leukaemic cells. In: Wybran J, Staquet MJ (eds) Clinical tumour immunology. Pergamon, Oxford
Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17:387–403
Graf T (2008) Blood lines redrawn. Nature 452:702–703
Brown G, Hughes P, Michell R et al (2008) Ordered commitment of hematopoietic stem cells to lineage fates. In: Burnsides WB, Ellsley RH (eds) Stem cell applications in disease and health. Nova Science Publishers, Inc., New York
Kondo M, Weissman IL, Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661–672
Akashi K, Traver D, Miyamoto T, Weissman IL (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404:193–197
Greaves M, Delia D, Robinson J et al (1981) Exploitation of monoclonal antibodies. A “who’s who” of haemopoietic malignanccy. Blood Cells 7:257–280
Krivtsov AV, Twomey D, Feng Z et al (2006) Transformation from committed progenitor to leukemia stem cell initiated by MLL-AF9. Nature 442:257–268
Somervaille TC, Cleary ML (2006) Identification and characterisation of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell 10:257–268
Fialkow PJ, Jaconson RJ, Papayannopoulou T (1997) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, eryrthrocyte, platelet and monocyte/macrophage. Am J Med 63:125–130
Bennett JM, Catovsky D, Daniel MT (1976) Proposals for the classification of the acute leukemias. French-American-British (FAB) co-operative group. Br J Haematol 33:451–458
Lenz G, Wright GW, Emre NC et al (2008) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 105:13520–13525
Ross ME, Zhou X, Song G et al (2003) Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 102:2951–2959
Yeoh EJ, Ross ME, Shurtkweff SA et al (2002) Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133–143
Kern W, Kohlmann A, Schnittger S et al (2004) Gene expression profiling as a diagnostic tool in acute myeloid leukemia. Am J Pharmacogenomics 4:225–237
Kohlmann A, Schoch C, Schnittger S et al (2004) Pediatric acute lymphoblastic leukemia (ALL) gene expression signatures classify an independent cohort of adult ALL patients. Leukemia 18:63–71
Downing JR, Wilson RK, Zhang J et al (2012) The pediatric cancer genome project. Nat Genet 44:619–622
Morin RD, Mungall K, Pleasance E et al (2013) Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood 122:1256–1265
Ceredig R, Rolink AG, Brown G (2009) Models of haematopoiesis: seeing the wood for the trees. Nat Rev Immunol 9:293–300
Velten L, Haas SF, Raffel S et al (2017) Human haematopoietic stem cell lineage commitment is a continuous process. Nat Cell Biol 19:271–281
Nestorowa S, Hamey FK, Pijuan Sala B et al (2006) A single-cell resolution map of mouse haematopoietic stem and progenitor cell differentiation. Blood 128:e20–e31
Koury MJ, Bondurant MC (1990) Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science 248:378–381
Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78:2791–2808
Metcalf D (1993) Haematopoietic regulators: redundancy or subtlety? Blood 82:3515–3523
Hume DA, MacDonald KP (2012) Therapeutic applications of macrophage colony-stimulating factor (CSF-1) and antagonists of CSF-1 recptor (CSF-1R) signaling. Blood 119:1810–1820
Gasson JC (1991) Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood 77:1131–1145
Shinjo K, Takeshita A, Higuchi M et al (1997) Erythropoietin receptor expression on human bone marrow erythroid precursor cells by a newly-devised quantitative flow-cytometric assay. Brit J Haematol 96:551–558
Mooney CJ, Cunningham A, Tsapogas P et al (2017) Selective expression of flt3 within the mouse haematopoietic stem cell compartment. Int J Mol Sci 18:E1037
Schuettpelz LG, Borgerding JN, Christopher MJ et al (2014) G-CSF regulates haematopoietic stem cell activity, in part, through activation of toll-like receptor signalling. Leukemia 28:1851–1860
Kondo M, Scherer DC, Miyamoto T et al (2000) Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature 407:383–386
Mossadegh-Keller N, Sarrazin S, Kandalla PK et al (2013) M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature 497:239–243
Ninos JM, Jefferies LC, Cogle CR et al (2006) The thrombopoietin receptor, cMpl, is a selective marker for human haematopoietic stem cells. J Transl Med 4:9
Notta F, Zandi S, Takayama N et al (2016) Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 351:aab2116
Balciunaite G, Ceredig R, Massa S et al (2005) A b220+ cd117+ cd19- haematopoietic progenitor with potent lymphoid and myeloid developmental potential. Eur J Immunol 35:2019–2030
Alberti-Servera L, von Muenchow L, Tsapogas P et al (2017) Single-cell RNA sequencing reveals developmental heterogeneity among early lymphoid progenitors. EMBO J 36:3619–3633
Grover A, Mancini E, Moore S et al (2014) Erythropoietin guides multipotent haematopoietic progenitor cells toward an erythroid fate. J Exp Med 211:181–188
Metcalf D, Burgess AW (1982) Clonal analysis of progenitor cell commitment of granulocyte or macrophage production. J Cell Physiol 111:275–283
Rieger MA, Hoppe PS, Smejkal BM et al (2009) Haematopoietic cytokines can instruct lineage choice. Science 325:217–218
Tsapogas P, Swee LK, Nusser A et al (2014) In vivo evidence for an instructive role of fms-like tyrosine kinase-3 (flt3) ligand in haematopoietic development. Haematologica 99:638–646
Balciunaite G, Ceredig R, Rolink AG (2005) The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer but no B-lymphocyte potential. Blood 105:1930–1936
Porritt HE, Rumfelt LL, Tabrizifard S et al (2004) Heterogeneity among dn1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20:735–745
Brown G, Tsapogas P, Ceredig R (2018) The changing face of haematopoiesis: a spectrum of options is available to stem cells. Immunol Cell Biol 96:898–911
Kikushige Y, Ishikawa F, Miyamoto T et al (2011) Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell 20:246–259
Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organised as a hierarchy that originates from a primitive haematopoietic cell. Nat Med 197:461–463
Cobaleda C, Sanchez-Garcia I (2009) B-cell acute lymphoblastic leukemia: towards understanding its cellular origin. BioEssays 31:600–660
Quintana E, Shackleton M, Sabel MS et al (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598
Vicente-Duenas C, Perez-Caro M, Abollo-Jimenez F et al (2009) Stem-cell driven cancer: “hands-off” regulation of cancer development. Cell Cycle 8:1314–1318
Vicente-Dueñas C, Romero-Camarero I, Cobaleda C et al (2013) Function of oncogenes in cancer development: a changing paradigm. EMBO J 32:1502–1513
Sachs L (1980) Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy. Proc Natl Acad Sci U S A 77:6152–6156
Brown G, Hughes PJ, Michell RH (2003) Cell differentiation and proliferation – simultaneous but independent? Exp Cell Res 291:282–288
Yates LR, Campbell PJ (2012) Evolution of the cancer genome. Nat Rev Genet 13:795–806
Ma Y, Dobbins SE, Sherborne AL et al (2013) Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 110:7429–7433
Castellanos A, Pintado B, Weruaga E et al (1997) A BCR-ABL(p190) fusion gene made by homologousrecombination causes B-cell acute lymphoblastic leukemias in chimeric mice with independence of the endogenous bcr product. Blood 90:2168–2174
García-Ramírez I, Bhatia S, Rodríguez-Hernández G et al (2018) Lmo2 expression defines tumor cell identity during T-cell leukemogenesis. EMBO J 37:e98783
Pérez-Caro M, Cobaleda C, González-Herrero I et al (2009) Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J 28:8–20
Greaves MF (1999) Molecular genetics, natural history and the demise of childhood leukemia. Eur J Cancer 35:173–185
Cox CV, Blair A (2005) A primitive cell origin for B-cell precursor ALL? Stem Cell Rev 1:189–196
Grimwade D, Enver T (2004) Acute promyelocytic leukemia: where does it stem from? Leukemia 18:375–384
Edwards RH, Wasik MA, Finan J et al (1999) Evidence for early haematopoietic progenitor cell involvement in acute promyelocytic leukemia. Am J Clin Pathol 112:819–827
Khan M, Siddiqui R, Naqvi K (2018) An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL). Ann Hematol 97:945–953
Kern W, Grossmann V, Roller A et al (2012) Mixed phenotype acute leukemia, T/myeloid, NOS(MPAL-TM) has a high DNMT3A mutation frequency and carries further genetic features of both AML and T-ALL: results of a comprehensive next-generation sequencing study analysing 32 genes. Blood 120:403
Mulligan C (2012) Molecular genetics of B-precursor acute lymphoblastic leukemia. J Clin Invest 122:3407–3416
Muschen M, Lee S, Zhou G (2002) Molecular portraits of B cell lineage commitment. PNAS 99:10014–10019
Yeoh E-J, Ross ME, Shurtleff SA (2002) Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133–143
Torrano V, Procter J, Cardus P et al (2011) ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor. Blood 118:4910–4918
de Lau WBM, Hurenkamp J, Berendes P et al (1998) The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1. Oncogene 17:503–510
Brach MA, Henschler R, Mertelsmann RH et al (1991) Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B. Pathobiology 59:284–288
Zhang D-E, Hetherington CJ, Chen H-M et al (1994) The macrophage transcription factor PU.1 directs tissue specific expression of the macrophage colony-stimulating factor receptor. MCB 14:373–381
Stanley ER, Chitu V (2014) CSF-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol 6:a021857
Dahl R, Walsh JC, Lanki D et al (2003) Regulation of macrophage and neutrophil fates by the PU.1:C/EBPα ratio and granulocyte colony-stimulating factor. Nat Immunol 4:1029–1036
Smith LT, Hohaus S, Gonzalez DA et al (1996) PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promotor in myeloid cells. Blood 88:1234–1247
Hohaus S, Petrovick MS, Voso MT et al (1995) PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene. MCB 15:5830–5845
Mizuki M, Schwable J, Steur C et al (2003) Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations. Blood 101:3164–3173
Volpe G, Clarke M, Garcìa P et al (2015) Regulation of the Flt3 Gene in haematopoietic stem and early progenitor cells. PLoS One 10:e0138257
Lowenberg B, Touw IP (1993) Hematopoeitc growth factors and their receptors in acute leukemia. Blood 81:281–292
Mueller BU, Pabst T, Osato M et al (2002) Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood 100:998–1007
Rosenbauer F, Wagner K, Kutok JL et al (2004) Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet 36:624–630
Antony-Defre I, Paul A, Leite J et al (2017) Pharmacological inhibition of the transcription factor PU.1 in leukemia. J Clin Invest 127:4297–4313
Pabst T, Mueller BU (2009) Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clin Cancer Res 15:5303–5307
Hackanson B, Bennett KL, Brena RM et al (2008) Epigenetic modification of CCAAT/enhancer binding protein alpha expression in acute myeloid leukemia. Cancer Res 68:3142–3151
Lee S, Chen J, Zhou G et al (2006) Gene expression profiles in acute myeloid leukemia with common translocations using SAGE. Proc Natl Acad Sci U S A 103:1030–1035
Xu Y, Milazzo JP, Somerville TDD et al (2018) A TFIID-SAGA perturbation that targets MYB and suppresses acute myeloid leukemia. Cancer Cell 33:13–28
Graham SM, Jorgensen HG, Allan E et al (2002) Primitive, quiescent Philadelphia positive stem cells from patients with chronic myeloid leukemia are insensitive to ST1571 in vitro. Blood 99:319–325
Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284
Riedell PA, Smith SM (2018) Should we use cell of origin and dual-protein expression in treating DLBCL. Clin Lymphoma Myeloma Leuk 18:91–97
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Brown, G. (2021). Introduction and Classification of Leukemias. In: Cobaleda, C., Sánchez-García, I. (eds) Leukemia Stem Cells. Methods in Molecular Biology, vol 2185. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0810-4_1
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DOI: https://doi.org/10.1007/978-1-0716-0810-4_1
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