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REVIEW ARTICLE - Molecular pathogenesis and novel treatments for CMML L. Marando et al.
Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616-3627.
22. Palomo L, Meggendorfer M, Hutter S, et al. Molecular landscape and clonal architecture of adult myelodysplastic/ myeloproliferative neoplasms. Blood. 2020;136(16):1851-1862.
23. Awada H, Nagata Y, Goyal A, et al. Invariant phenotype and molecular association of biallelic TET2 mutant myeloid neoplasia. Blood Adv. 2019;3(3):339-349.
24. Rasmussen KD, Jia G, Johansen JV, et al. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev. 2015;29(9):910-922.
25. Ito K, Lee J, Chrysanthou S, et al. Non-catalytic roles of Tet2 are essential to regulate hematopoietic stem and progenitor cell homeostasis. Cell Rep. 2019;28(10):2480-2490.e4.
26. Li Z, Cai X, Cai CL, et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood. 2011;118(17):4509-4518.
27. Ostrander EL, Kramer AC, Mallaney C, et al. Divergent effects of Dnmt3a and Tet2 mutations on hematopoietic progenitor cell fitness. Stem Cell Rep. 2020;14(4):551-560.
28. Jakobsen NA, Turkalj S, Zeng AGX, et al. Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging. Cell Stem Cell. 2024;31(8):1127-1144.
29. Zhang J, Lieu YK, Ali AM, et al. Disease-associated mutation in SRSF2 misregulates splicing by altering RNA-binding affinities. Proc Natl Acad Sci U S A. 2015;112(34):E4726-4734.
30. Kim E, Ilagan JO, Liang Y, et al. SRSF2 mutations contribute to myelodysplasia by mutant-specific effects on exon recognition. Cancer Cell. 2015;27(5):617-630.
31. Kon A, Yamazaki S, Nannya Y, et al. Physiological Srsf2 P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice. Blood. 2018;131(6):621-635.
32. Smeets MF, Tan SY, Xu JJ, et al. Srsf2P95H initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells. Blood. 2018;132(6):608-621.
33. Gelsi-Boyer V, Trouplin V, Adélaïde J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145(6):788-800.
34. Abdel-Wahab O, Adli M, LaFave LM, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2- mediated gene repression. Cancer Cell. 2012;22(2):180-193.
35. Asada S, Goyama S, Inoue D, et al. Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nat Commun. 2018;9(1):2733.
36. Campagne A, Lee MK, Zielinski D, et al. BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation. Nat Commun. 2019;10(1):348.
37. Binder M, Carr RM, Lasho TL, et al. Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1- mutant chronic myelomonocytic leukemia. Nat Commun. 2022;13(1):1434.
38. Carr RM, Vorobyev D, Lasho T, et al. RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A- PLK1 axis. Nat Commun. 2021;12(1):2901.
39. Bezerra ED, Lasho TL, Finke CM, et al. CSF3R T618I mutant chronic myelomonocytic leukemia (CMML) defines a proliferative CMML subtype enriched in ASXL1 mutations with
adverse outcomes. Blood Cancer J. 2021;11(3):54.
40. Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC,
Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A. 2014;111(7):2548-2553.
41. Shlush LI, Zandi S, Mitchell A, et al. Identification of pre- leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328-333.
42. Lasho T, Patnaik MM. Juvenile myelomonocytic leukemia - a bona fide RASopathy syndrome. Best Pract Res Clin Haematol. 2020;33(2):101171.
43. Li Q, Bohin N, Wen T, et al. Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness. Nature. 2013;504(7478):143-147.
44. Hérault A, Binnewies M, Leong S, et al. Myeloid progenitor cluster formation drives emergency and leukaemic myelopoiesis. Nature. 2017;544(7648):53-58.
45. Ferrall-Fairbanks MC, Dhawan A, Johnson B, et al. Progenitor hierarchy of chronic myelomonocytic leukemia identifies inflammatory monocytic-biased trajectory linked to worse outcomes. Blood Cancer Discov. 2022;3(6):536-553.
46. Hamarsheh S, Osswald L, Saller BS, et al. Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation. Nat Commun. 2020;11(1):1659.
47. Hurtado-Navarro L, Cuenca-Zamora EJ, Zamora L, et al. NLRP3 inflammasome activation and symptom burden in KRAS- mutated CMML patients is reverted by IL-1 blocking therapy. Cell Rep Med. 2023;4(12):101329.
48. Broz P, Pelegrín P, Shao F. The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2020;20(3):143-157.
49. Baroja-Mazo A, Martín-Sánchez F, Gomez AI, et al. The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 2014;15(8):738-748.
50. Franklin BS, Bossaller L, De Nardo D, et al. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat Immunol. 2014;15(8):727-737.
51. Schmid MC, Avraamides CJ, Dippold HC, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kg, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011;19(6):715-727.
52. Moore AR, Rosenberg SC, McCormick F, Malek S. RAS-targeted therapies: is the undruggable drugged? Nat Rev Drug Discov. 2020;19(8):533-552.
53. You X, Liu F, Binder M, et al. Asxl1 loss cooperates with oncogenic Nras in mice to reprogram the immune microenvironment and drive leukemic transformation. Blood. 2022;139(7):1066-1079.
54. Lucas N, Duchmann M, Rameau P, et al. Biology and prognostic impact of clonal plasmacytoid dendritic cells in chronic myelomonocytic leukemia. Leukemia. 2019;33(10):2466-2480.
55. Mangaonkar AA, Reichard KK, Binder M, et al. Bone marrow dendritic cell aggregates associate with systemic immune dysregulation in chronic myelomonocytic leukemia. Blood Adv. 2020;4(21):5425-5430.
56. Munn DH, Mellor AL. IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol. 2016;37(3):193-207.
57. Munn DH, Zhou M, Attwood JT, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281(5380):1191-1193.
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