An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis

Nature Communications

Volumn 6, Issue , 2015, Pages

  Jung, Namyoung ^a   Dai, Bo ^b   Gentles, Andrew J ^c   Majeti, Ravindra ^b   Feinberg, Andrew P ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b STANFORD CANCER INSTITUTE   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER; CYTOGENETICS; DNA; GENE EXPRESSION; GENETIC ANALYSIS; METHYLATION; MUTATION; PATHOGEN; RODENT; SUBPOPULATION;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER PROGNOSIS; CANCER STEM CELL; COLONY FORMING UNIT GM; CONTROLLED STUDY; CYTOGENETICS; DNA METHYLATION; EPIGENETICS; FEMALE; GENE; GENE CLUSTER; GENE EXPRESSION; GENE MUTATION; GENETIC ANALYSIS; HOXA GENE; HUMAN; HUMAN CELL; LEUKEMIA CELL; LEUKEMIA STEM CELL; MODIFIER GENE; MOUSE; NONHUMAN; PATHOGENESIS; TUMOR XENOGRAFT; ACUTE MYELOID LEUKEMIA; ANIMAL; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; MUTATION; PATHOLOGY; PHYSIOLOGY;

MUS;

HOMEODOMAIN PROTEIN; HOXA PROTEIN;

ANIMALS; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HOMEODOMAIN PROTEINS; LEUKEMIA, MYELOID, ACUTE; MICE; MUTATION; NEOPLASTIC STEM CELLS;

EID: 84943616457     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9489     Document Type: Article

References (46)

1. Lowenberg, B., Downing, J. R. & Burnett, A. Acute myeloid leukemia. N. Engl. J. Med. 341, 1051-1062 (1999).
2. Majeti, R. Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene 30, 1009-1019 (2011).
3. Goardon, N. et al. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell 19, 138-152 (2011).
4. Sarry, J. E. et al. Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rgammac-deficient mice. J. Clin. Invest. 121, 384-395 (2011).
5. Eppert, K. et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat. Med. 17, 1086-1093 (2011).
6. Gentles, A. J., Plevritis, S. K., Majeti, R. & Alizadeh, A. A. Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA 304, 2706-2715 (2010).
7. Issa, J. P. DNA methylation as a clinical marker in oncology. J. Clin. Oncol. 30, 2566-2568 (2012).
8. Heuser, M. et al. Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex. Cancer Cell 20, 39-52 (2011).
9. Krivtsov, A. V. et al. Cell of origin determines clinically relevant subtypes of MLL-rearranged AML. Leukemia 27, 852-860 (2013).
10. Kreso, A. & Dick, J. E. Evolution of the cancer stem cell model. Cell Stem Cell 14, 275-291 (2014).
11. Corces-Zimmerman, M. R., Hong, W. J., Weissman, I. L., Medeiros, B. C. & Majeti, R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc. Natl Acad. Sci. USA 111, 2548-2553 (2014).
12. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci. Transl. Med. 4, 149ra118 (2012).
13. Shlush, L. I. et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506, 328-333 (2014).
14. Jamieson, C. H. et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med. 351, 657-667 (2004).
15. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059-2074 (2013).
16. Abdel-Wahab, O. et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 22, 180-193 (2012).
17. Figueroa, M. E. et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18, 553-567 (2010).
18. Bartholdy, B. et al. HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia. J. Clin. Invest. 124, 1158-1167 (2014).
19. Losada, A. Cohesin in cancer: chromosome segregation and beyond. Nat. Rev. Cancer 14, 389-393 (2014).
20. Thol, F. et al. Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications. Blood 123, 914-920 (2014).
21. Thorsteinsdottir, U. et al. Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood 99, 121-129 (2002).
22. Chung, K. Y. et al. Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation. Cancer Res. 66, 11781-11791 (2006).
23. Takeda, A., Goolsby, C. & Yaseen, N. R. NUP98-HOXA9 induces long-term proliferation and blocks differentiation of primary human CD34+ hematopoietic cells. Cancer Res. 66, 6628-6637 (2006).
24. Lehnertz, B. et al. The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev. 28, 317-327 (2014).
25. Milne, T. A. et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol. Cell 10, 1107-1117 (2002).
26. Drabkin, H. A. et al. Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia 16, 186-195 (2002).
27. Samudio, I. et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J. Clin. Invest. 120, 142-156 (2010).
28. Vassiliou, G. S. et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat. Genet. 43, 470-475 (2011).
29. Dufour, A. et al. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J. Clin. Oncol. 28, 570-577 (2010).
30. Metzeler, K. H. et al. An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 112, 4193-4201 (2008).
31. Valk, P. J. et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N. Engl. J. Med. 350, 1617-1628 (2004).
32. Wouters, B. J. et al. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113, 3088-3091 (2009).
33. Wilson, C. S. et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 108, 685-696 (2006).
34. Benetatos, L. et al. The micro RNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis. Cell. Mol. Life Sci. 70, 795-814 (2013).
35. Ji, H. et al. Comprehensive methylome map of lineage commitment from haematopoietic progenitors. Nature 467, 338-342 (2010).
36. Irizarry, R. A. et al. The human colon cancer methylome shows similar hypoand hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet. 41, 178-186 (2009).
37. Hansen, K. D. et al. Increased methylation variation in epigenetic domains across cancer types. Nat. Genet. 43, 768-775 (2011).
38. Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3, 730-737 (1997).
39. Lapidot, T. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645-648 (1994).
40. Estey, E. H. Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia. Leukemia 27, 1803-1812 (2013).
41. Alharbi, R. A., Pettengell, R., Pandha, H. S. & Morgan, R. The role of HOX genes in normal hematopoiesis and acute leukemia. Leukemia 27, 1000-1008 (2013).
42. Nakamura, T. et al. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat. Genet. 12, 154-158 (1996).
43. Golub, T. R. et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531-537 (1999).
44. Bach, C. et al. Leukemogenic transformation by HOXA cluster genes. Blood 115, 2910-2918 (2010).
45. Aryee, M. J. et al. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30, 1363-1369 (2014).
46. Jaffe, A. E. et al. Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies. Int. J. Epidemiol. 41, 200-209 (2012).