Mel Greaves

Summary

Affiliation: Institute of Cancer Research
Country: UK

Publications

  1. ncbi request reprint Leukemia in twins: lessons in natural history
    Mel F Greaves
    Leukemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Rd, London SW3 6JB, United Kingdom
    Blood 102:2321-33. 2003
  2. ncbi request reprint Origins of chromosome translocations in childhood leukaemia
    Mel F Greaves
    LRF Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Cancer 3:639-49. 2003
  3. ncbi request reprint Cancer stem cells: back to Darwin?
    Mel Greaves
    Section of Haemato oncology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Semin Cancer Biol 20:65-70. 2010
  4. pmc Cancer stem cells as 'units of selection'
    Mel Greaves
    Division of Molecular Pathology, Haemato Oncology Research Unit, The Institute of Cancer Research Sutton, UK
    Evol Appl 6:102-8. 2013
  5. pmc Clonal expansion in B-CLL: fungal drivers or self-service?
    Mel Greaves
    Division of Molecular Pathology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, England, UK
    J Exp Med 210:1-3. 2013
  6. ncbi request reprint In utero origins of childhood leukaemia
    Mel Greaves
    Chester Beatty Laboratories, Institute of Cancer Research, Section of Haemato oncology, 237 Fulham Road, London SW3 6JB, United Kingdom
    Early Hum Dev 81:123-9. 2005
  7. ncbi request reprint Infection, immune responses and the aetiology of childhood leukaemia
    Mel Greaves
    The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Nat Rev Cancer 6:193-203. 2006
  8. ncbi request reprint Darwinian medicine: a case for cancer
    Mel Greaves
    Section of Haemato oncology, The Institute of Cancer Research, London, UK
    Nat Rev Cancer 7:213-21. 2007
  9. ncbi request reprint Pre-natal origins of childhood leukemia
    Mel Greaves
    Leukaemia Research Fund Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Rev Clin Exp Hematol 7:233-45. 2003
  10. pmc Clonal evolution in cancer
    Mel Greaves
    Division of Molecular Pathology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Nature 481:306-13. 2012

Collaborators

Detail Information

Publications47

  1. ncbi request reprint Leukemia in twins: lessons in natural history
    Mel F Greaves
    Leukemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Rd, London SW3 6JB, United Kingdom
    Blood 102:2321-33. 2003
    ..We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms...
  2. ncbi request reprint Origins of chromosome translocations in childhood leukaemia
    Mel F Greaves
    LRF Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Nat Rev Cancer 3:639-49. 2003
    ..How, when and where do translocations arise? And can these insights aid our understanding of the natural history, pathogenesis and causes of leukaemia?..
  3. ncbi request reprint Cancer stem cells: back to Darwin?
    Mel Greaves
    Section of Haemato oncology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Semin Cancer Biol 20:65-70. 2010
    ..In this, cells with self-renewal potency or 'stem-ness' provide genetically diverse units of evolutionary selection in cancer progression. The model has significant implications for targeted cancer therapy...
  4. pmc Cancer stem cells as 'units of selection'
    Mel Greaves
    Division of Molecular Pathology, Haemato Oncology Research Unit, The Institute of Cancer Research Sutton, UK
    Evol Appl 6:102-8. 2013
    ..These cells drive evolutionary progression of disease and provide reservoirs for relapse or recurrence and drug resistance. They represent the prime, but elusive and moving, targets for therapeutic control...
  5. pmc Clonal expansion in B-CLL: fungal drivers or self-service?
    Mel Greaves
    Division of Molecular Pathology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, England, UK
    J Exp Med 210:1-3. 2013
    ..Another study, in contrast, suggests that B-CLL cells uniquely acquire the ability to signal in the complete absence of ligand...
  6. ncbi request reprint In utero origins of childhood leukaemia
    Mel Greaves
    Chester Beatty Laboratories, Institute of Cancer Research, Section of Haemato oncology, 237 Fulham Road, London SW3 6JB, United Kingdom
    Early Hum Dev 81:123-9. 2005
    ..These natural histories provide an important framework for consideration of key aetiological events in paediatric leukaemia...
  7. ncbi request reprint Infection, immune responses and the aetiology of childhood leukaemia
    Mel Greaves
    The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Nat Rev Cancer 6:193-203. 2006
    ..Although there might not be a single or exclusive cause, an abnormal immune response to common infection(s) has emerged as a plausible aetiological mechanism...
  8. ncbi request reprint Darwinian medicine: a case for cancer
    Mel Greaves
    Section of Haemato oncology, The Institute of Cancer Research, London, UK
    Nat Rev Cancer 7:213-21. 2007
    ....
  9. ncbi request reprint Pre-natal origins of childhood leukemia
    Mel Greaves
    Leukaemia Research Fund Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Rev Clin Exp Hematol 7:233-45. 2003
    ..These natural histories provide an important framework for consideration of key etiological events in pediatric leukemia...
  10. pmc Clonal evolution in cancer
    Mel Greaves
    Division of Molecular Pathology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Nature 481:306-13. 2012
    ..The inherently Darwinian character of cancer is the primary reason for this therapeutic failure, but it may also hold the key to more effective control...
  11. doi request reprint Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
    Gabriele Migliorini
    Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Blood 122:3298-307. 2013
    ..0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development. ..
  12. pmc The TEL-AML1 leukemia fusion gene dysregulates the TGF-beta pathway in early B lineage progenitor cells
    Anthony M Ford
    Section of Haemato oncology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
    J Clin Invest 119:826-36. 2009
    ..Collectively, these data suggest a plausible mechanism by which dysregulated immune responses to infection might promote the malignant evolution of TEL-AML1-expressing preleukemic clones...
  13. ncbi request reprint The small oligomerization domain of gephyrin converts MLL to an oncogene
    Mariko Eguchi
    Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom
    Blood 103:3876-82. 2004
    ..Our results, and other recent data, provide a mechanism for oncogenic conversion of MLL by fusion partners encoding cytoplasmic proteins...
  14. ncbi request reprint MLL chimeric protein activation renders cells vulnerable to chromosomal damage: an explanation for the very short latency of infant leukemia
    Mariko Eguchi
    Section of Haemato oncology, The Institute of Cancer Research, London, UK
    Genes Chromosomes Cancer 45:754-60. 2006
    ..This phenotype is associated with an altered pattern of cell cycle arrest and/or apoptosis...
  15. doi request reprint Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia
    Caroline M Bateman
    Section of Haemato oncology, The Institute of Cancer Research, Surrey, UK
    Blood 115:3553-8. 2010
    ..These data place all "driver" CNAs secondary to the prenatal gene fusion event and most probably postnatal in the sequential, molecular pathogenesis of ALL...
  16. ncbi request reprint Genome-wide homozygosity signatures and childhood acute lymphoblastic leukemia risk
    Fay J Hosking
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Blood 115:4472-7. 2010
    ..Our findings make it unlikely that levels of measured homozygosity, caused by autozygosity, uniparental isodisomy, or hemizygosity, play a major role in defining BCP-ALL risk in predominantly outbred populations...
  17. doi request reprint Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia
    Frederik W van Delft
    Section of Haemato oncology, Institute of Cancer Research, Sutton, UK
    Blood 117:6247-54. 2011
    ....
  18. ncbi request reprint Molecular pathogenesis of MLL-associated leukemias
    Mariko Eguchi
    Section of Haemato oncology, Institute of Cancer Research, London, UK
    Int J Hematol 82:9-20. 2005
    ..Further elaboration of the biology of MLL gene-associated leukemia should lead to novel and specific therapeutic strategies...
  19. pmc Single-cell mutational profiling and clonal phylogeny in cancer
    Nicola E Potter
    The Institute of Cancer Research, London, SM2 5NG, United Kingdom
    Genome Res 23:2115-25. 2013
    ..We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies. ..
  20. doi request reprint MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia
    Fay J Hosking
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom
    Blood 117:1633-40. 2011
    ..We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL...
  21. doi request reprint Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia
    Lyndal Kearney
    Section of Haemato oncology, The Institute of Cancer Research, Sutton, United Kingdom
    Blood 113:646-8. 2009
    ..These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events...
  22. doi request reprint Genetic variegation of clonal architecture and propagating cells in leukaemia
    Kristina Anderson
    Section of Haemato oncology, The Institute of Cancer Research, Sutton SM2 5NG, UK
    Nature 469:356-61. 2011
    ..These data have implications for cancer genomics and for the targeted therapy of cancer...
  23. doi request reprint ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a dysregulated erythropoietin receptor
    Verónica Torrano
    Haemato Oncology Research Unit, Division of Molecular Pathology, Institute of Cancer Research, Sutton, UK
    Blood 118:4910-8. 2011
    ..These data support the contention that ETV6-RUNX1 directly activates ectopic expression of a functional EPOR and provides cell survival signals that may contribute critically to persistence of covert premalignant clones in children...
  24. doi request reprint Genetic lesions in a preleukemic aplasia phase in a child with acute lymphoblastic leukemia
    Sharon W Horsley
    Section of Haemato oncology, The Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey, UK
    Genes Chromosomes Cancer 47:333-40. 2008
    ..These data have implications for the biology of ALL and for management of similar patients...
  25. pmc Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia
    Amy L Sherborne
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    Haematologica 96:1049-54. 2011
    ..Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium...
  26. doi request reprint Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia
    Elli Papaemmanuil
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    Nat Genet 41:1006-10. 2009
    ..Notably, all three risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors...
  27. pmc Directing oncogenic fusion genes into stem cells via an SCL enhancer
    Mariko Eguchi
    Section of Haemato oncology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom
    Proc Natl Acad Sci U S A 102:1133-8. 2005
    ..These data indicate that related oncogenic fusion proteins similarly expressed in a hierarchy of early stem cells can have selective, cell type-specific developmental impacts...
  28. ncbi request reprint Protracted postnatal natural histories in childhood leukemia
    Ana Teresa Maia
    LRF Centre, Institute of Cancer Research, London, United Kingdom
    Genes Chromosomes Cancer 39:335-40. 2004
    ..We present evidence that the duration of the postnatal preleukemic state can occasionally be very protracted in these biological subtypes of pediatric leukemia, and we discuss its biological significance...
  29. ncbi request reprint TEL deletion analysis supports a novel view of relapse in childhood acute lymphoblastic leukemia
    Jan Zuna
    Leukemia Research Fund Centre for Cell and Molecular Biology, Institute of Cancer Research, London, United Kingdom
    Clin Cancer Res 10:5355-60. 2004
    ..This consistent sequence of molecular pathogenesis facilitates an analysis of the clonal origins of relapse in this leukemia, which has some unusual clinical features...
  30. ncbi request reprint Prenatal chromosomal diversification of leukemia in monozygotic twins
    Helena Kempski
    Molecular Haematology Unit, Institute of Child Health, London, United Kingdom
    Genes Chromosomes Cancer 37:406-11. 2003
    ..This case of leukemia illustrates in utero initiation with early imposition of chromosomal instability, the progressively divergent evolution of which can be mapped in the twins into pre- and postnatal periods...
  31. pmc Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk
    Amy L Sherborne
    Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    Nat Genet 42:492-4. 2010
    ..3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 x 10(-11)), irrespective of cell lineage...
  32. ncbi request reprint The role of the MLL gene in infant leukemia
    Mariko Eguchi
    LRF Centre for Cell and Molecular Biology of Leukaemia, Institute of Cancer Research, London, UK
    Int J Hematol 78:390-401. 2003
    ..We review here progress in tackling these questions...
  33. ncbi request reprint NOTCH1 mutation can be an early, prenatal genetic event in T-ALL
    Minenori Eguchi-Ishimae
    Section of Haemato oncology, Institute of Cancer Research, London
    Blood 111:376-8. 2008
    ..We conclude that NOTCH1 can be an early or initiating event in T-ALL arising prenatally, to be complemented by a postnatal SIL-TAL1 fusion...
  34. pmc Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemia
    Yussanne Ma
    Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom
    Proc Natl Acad Sci U S A 110:7429-33. 2013
    ..These changes occurred in a background of noncoding mutational changes that were almost entirely discordant in twin pairs and likely passenger mutations acquired during leukemic cell proliferation...
  35. ncbi request reprint The association of a distinctive allele of NAD(P)H:quinone oxidoreductase with pediatric acute lymphoblastic leukemias with MLL fusion genes in Japan
    Minenori Eguchi-Ishimae
    Section of Haemato oncology, Institute of Cancer Research, London, UK
    Haematologica 90:1511-5. 2005
    ..Previous studies in Caucasian populations have provided evidence that a loss of function allele at nt 609 (C609T, Pro187Ser) is associated with increased risk of infant acute lymphoblastic leukemia (ALL) with MLL-AF4 fusion genes...
  36. doi request reprint Tyrosine kinase inhibitor insensitivity of non-cycling CD34+ human acute myeloid leukaemia cells with FMS-like tyrosine kinase 3 mutations
    Caroline L Alvares
    Section of Haemato oncology, The Institute of Cancer Research, Sutton, Surrey Department of Clinical Cytogenetics, The Royal Marsden Hospital, Sutton, Surrey
    Br J Haematol 154:457-65. 2011
    ..These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted...
  37. ncbi request reprint Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood
    Ana Teresa Maia
    LRF Centre, Institute of Cancer Research, London, UK
    Genes Chromosomes Cancer 40:38-43. 2004
    ..Now, however, we can provide direct evidence of this from our identification of CD34+/CD19+ B-lineage progenitor cells with triploid chromosomes in the stored cord blood of an individual who subsequently developed hyperdiploid ALL...
  38. ncbi request reprint Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia
    Arthur Zelent
    Section of Haematological Oncology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK
    Oncogene 23:4275-83. 2004
    ....
  39. pmc Chromosome translocations and covert leukemic clones are generated during normal fetal development
    Hiroshi Mori
    Leukaemia Research Fund Centre for Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK
    Proc Natl Acad Sci U S A 99:8242-7. 2002
    ..The frequency of positive cells (10(-4) to 10(-3)) indicates substantial clonal expansion of a progenitor population. These data have significant implications for the pathogenesis, natural history, and etiology of childhood leukemia...
  40. ncbi request reprint Cancer causation: the Darwinian downside of past success?
    Mel Greaves
    Cell Biology and the Leukaemia Research Fund Centre for Cell and Molecular Biology, Institute of Cancer Research, London, UK
    Lancet Oncol 3:244-51. 2002
    ..A case is made here for a Darwinian perspective on breast and prostate cancers, for which current understanding of causation is limited and contentious...
  41. pmc Childhood leukaemia
    Mel Greaves
    Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB
    BMJ 324:283-7. 2002
  42. ncbi request reprint The histone deacetylase 9 gene encodes multiple protein isoforms
    Kevin Petrie
    Leukemia Research Fund Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    J Biol Chem 278:16059-72. 2003
    ..These results suggest that HDAC9 plays a role in hematopoiesis; its deregulated expression may be associated with some human cancers...
  43. pmc Patterns of somatic mutation in human cancer genomes
    Christopher Greenman
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 446:153-8. 2007
    ..Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated...
  44. ncbi request reprint Is the timing of exposure to infection a major determinant of acute lymphoblastic leukaemia in Hong Kong?
    Li Chong Chan
    Haematology Section, Department of Pathology, University of Hong Kong, Hong Kong
    Paediatr Perinat Epidemiol 16:154-65. 2002
    ..These results provide support for the delayed exposure hypothesis in an affluent geographical setting in which population exposure to infectious agents is quite distinct from the settings of previous case-control studies...