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ATRA-Induced Cellular Differentiation and CD38 Expression Inhibits Acquisition of BCR-ABL Mutations for CML Acquired Resistance


Acquired resistance through genetic mutations is a major mechanism for cancer drug resistance and accounts for the short life of targeted therapy in several types of human cancer. Mechanistically, however, very little is understood about how resistant mutations are actually acquired during cancer therapy. In this manuscript, we used chronic myelogenous leukemia (CML) as a disease model and showed that mutation acquisition process is accompanied by global genome transcriptional reprogramming and reduction of cellular differentiation status. Forced cell differentiation by all-trans retinoic acid (ATRA) potently blocks acquisition of genetic mutations and CML acquired resistance. ATRA effect is mediated, in part, through stimulating CD38 gene expression, which reduces cellular cofactor nicotinamide adenine dinucleotide (NAD+) content and thus the activity of NAD+-dependent protein deacetylase SIRT1 that promotes error-prone DNA damage repair and mutagenesis. Our findings provide novel insight of mutation acquisition process during targeted therapy for CML. This study has translational implication in clinical treatment of CML, and perhaps other malignancies, by combining a differentiation agent to overcome mutation-mediated drug resistance if possible.


Vyšlo v časopise: ATRA-Induced Cellular Differentiation and CD38 Expression Inhibits Acquisition of BCR-ABL Mutations for CML Acquired Resistance. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004414
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004414

Souhrn

Acquired resistance through genetic mutations is a major mechanism for cancer drug resistance and accounts for the short life of targeted therapy in several types of human cancer. Mechanistically, however, very little is understood about how resistant mutations are actually acquired during cancer therapy. In this manuscript, we used chronic myelogenous leukemia (CML) as a disease model and showed that mutation acquisition process is accompanied by global genome transcriptional reprogramming and reduction of cellular differentiation status. Forced cell differentiation by all-trans retinoic acid (ATRA) potently blocks acquisition of genetic mutations and CML acquired resistance. ATRA effect is mediated, in part, through stimulating CD38 gene expression, which reduces cellular cofactor nicotinamide adenine dinucleotide (NAD+) content and thus the activity of NAD+-dependent protein deacetylase SIRT1 that promotes error-prone DNA damage repair and mutagenesis. Our findings provide novel insight of mutation acquisition process during targeted therapy for CML. This study has translational implication in clinical treatment of CML, and perhaps other malignancies, by combining a differentiation agent to overcome mutation-mediated drug resistance if possible.


Zdroje

1. MeloJV, BarnesDJ (2007) Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer 7: 441–453.

2. DeiningerMW, DrukerBJ (2003) Specific targeted therapy of chronic myelogenous leukemia with imatinib. Pharmacol Rev 55: 401–423.

3. BhatiaR, HoltzM, NiuN, GrayR, SnyderDS, et al. (2003) Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 101: 4701–4707.

4. HuY, SwerdlowS, DuffyTM, WeinmannR, LeeFY, et al. (2006) Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci U S A 103: 16870–16875.

5. GorreME, MohammedM, EllwoodK, HsuN, PaquetteR, et al. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876–880.

6. ShahNP, NicollJM, NagarB, GorreME, PaquetteRL, et al. (2002) Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2: 117–125.

7. KantarjianH, GilesF, WunderleL, BhallaK, O'BrienS, et al. (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 354: 2542–2551.

8. ShahNP, TranC, LeeFY, ChenP, NorrisD, et al. (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305: 399–401.

9. TalpazM, ShahNP, KantarjianH, DonatoN, NicollJ, et al. (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354: 2531–2541.

10. O'HareT, ShakespeareWC, ZhuX, EideCA, RiveraVM, et al. (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16: 401–412.

11. YuanH, WangZ, GaoC, ChenW, HuangQ, et al. (2010) BCR-ABL gene expression is required for its mutations in a novel KCL-22 cell culture model for acquired resistance of chronic myelogenous leukemia. J Biol Chem 285: 5085–5096.

12. WangZ, YuanH, RothM, StarkJM, BhatiaR, et al. (2013) SIRT1 deacetylase promotes acquisition of genetic mutations for drug resistance in CML cells. Oncogene 32: 589–598.

13. YuanH, WangZ, ZhangH, RothM, BhatiaR, et al. (2012) Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model. Carcinogenesis 33: 285–293.

14. Chen WY, Yuan H, Wang Z (2011) De novo acquisition of BCR-ABL mutations for CML acquired resistance. In: Koschmieder S, Krug U, editors. Myeloid Leukemia: Basic Mechanisms of Leukemogenesis INTECH. pp. 69–84.

15. TallmanMS, AndersenJW, SchifferCA, AppelbaumFR, FeusnerJH, et al. (1997) All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 337: 1021–1028.

16. WarrellRPJr, FrankelSR, MillerWHJr, ScheinbergDA, ItriLM, et al. (1991) Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 324: 1385–1393.

17. MalavasiF, DeaglioS, FunaroA, FerreroE, HorensteinAL, et al. (2008) Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev 88: 841–886.

18. RadichJP, DaiH, MaoM, OehlerV, SchelterJ, et al. (2006) Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A 103: 2794–2799.

19. SubramanianA, TamayoP, MoothaVK, MukherjeeS, EbertBL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102: 15545–15550.

20. HuangF, ReevesK, HanX, FairchildC, PlateroS, et al. (2007) Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer Res 67: 2226–2238.

21. KangHC, KimIJ, ParkJH, ShinY, KuJL, et al. (2004) Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarrays. Clin Cancer Res 10: 272–284.

22. KauffmannA, RosselliF, LazarV, WinnepenninckxV, Mansuet-LupoA, et al. (2008) High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 27: 565–573.

23. DashAB, WilliamsIR, KutokJL, TomassonMH, AnastasiadouE, et al. (2002) A murine model of CML blast crisis induced by cooperation between BCR/ABL and NUP98/HOXA9. Proc Natl Acad Sci U S A 99: 7622–7627.

24. KroonE, ThorsteinsdottirU, MayotteN, NakamuraT, SauvageauG (2001) NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice. Embo J 20: 350–361.

25. TakedaA, GoolsbyC, YaseenNR (2006) NUP98-HOXA9 induces long-term proliferation and blocks differentiation of primary human CD34+ hematopoietic cells. Cancer Res 66: 6628–6637.

26. GrahamSM, VassJK, HolyoakeTL, GrahamGJ (2007) Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources. Stem Cells 25: 3111–3120.

27. KubonishiI, MiyoshiI (1983) Establishment of a Ph1 chromosome-positive cell line from chronic myelogenous leukemia in blast crisis. Int J Cell Cloning 1: 105–117.

28. DrachJ, McQueenT, EngelH, AndreeffM, RobertsonKA, et al. (1994) Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor-alpha. Cancer Res 54: 1746–1752.

29. LamkinTJ, ChinV, VarvayanisS, SmithJL, SramkoskiRM, et al. (2006) Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels. J Cell Biochem 97: 1328–1338.

30. WiernikPH, DutcherJP, PaiettaE, HittelmanWN, VyasR, et al. (1991) Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid. Leukemia 5: 504–509.

31. NilssonB, OlofssonT, OlssonI (1984) Myeloid Differentiation in Liquid Cultures of Cells from Patients with Chronic Myeloid-Leukemia - Effects of Retinoic Acid and Indomethacin. Experimental Hematology 12: 91–99.

32. AksoyP, WhiteTA, ThompsonM, ChiniEN (2006) Regulation of intracellular levels of NAD: a novel role for CD38. Biochem Biophys Res Commun 345: 1386–1392.

33. AksoyP, EscandeC, WhiteTA, ThompsonM, SoaresS, et al. (2006) Regulation of SIRT 1 mediated NAD dependent deacetylation: a novel role for the multifunctional enzyme CD38. Biochem Biophys Res Commun 349: 353–359.

34. ChuS, XuH, ShahNP, SnyderDS, FormanSJ, et al. (2005) Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment. Blood 105: 2093–2098.

35. SchemionekM, EllingC, SteidlU, BaumerN, HamiltonA, et al. (2010) BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells. Blood 115: 3185–3195.

36. BrunsI, CzibereA, FischerJC, RoelsF, CadedduRP, et al. (2009) The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence. Leukemia 23: 892–899.

37. YuanH, WangZ, LiL, ZhangH, ModiH, et al. (2012) Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood 119: 1904–1914.

38. SequistLV, WaltmanBA, Dias-SantagataD, DigumarthyS, TurkeAB, et al. (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3: 75ra26.

39. CollinsSJ (2002) The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 16: 1896–1905.

40. PurtonLE, BernsteinID, CollinsSJ (2000) All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. Blood 95: 470–477.

41. ChenZ, WangZY, ChenSJ (1997) Acute promyelocytic leukemia: cellular and molecular basis of differentiation and apoptosis. Pharmacol Ther 76: 141–149.

42. DutcherJP, LeeS, GallagherRE, MakaryAZ, HinesJD, et al. (2005) Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia: a study of the Eastern Cooperative Oncology Group (E1993). Leuk Lymphoma 46: 377–385.

43. EgyedM, KollarB, RumiG, KellerE, VassJ, et al. (2003) Effect of retinoic acid treatment on cytogenetic remission of chronic myeloid leukaemia. Acta Haematol 109: 84–89.

44. CortesJ, KantarjianH, O'BrienS, BeranM, EsteyE, et al. (1997) A pilot study of all-trans retinoic acid in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Leukemia 11: 929–932.

45. AdamsonPC (1996) All-Trans-Retinoic Acid Pharmacology and Its Impact on the Treatment of Acute Promyelocytic Leukemia. Oncologist 1: 305–314.

46. PengB, LloydP, SchranH (2005) Clinical pharmacokinetics of imatinib. Clin Pharmacokinet 44: 879–894.

47. AlessioM, RoggeroS, FunaroA, De MonteLB, PeruzziL, et al. (1990) CD38 molecule: structural and biochemical analysis on human T lymphocytes, thymocytes, and plasma cells. J Immunol 145: 878–884.

48. TerstappenLW, HuangS, SaffordM, LansdorpPM, LokenMR (1991) Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Blood 77: 1218–1227.

49. Kapil Mehta FM, editor (2000) Human CD38 and Related Molecules: Chemical Immunology.

50. PrusE, FibachE (2003) Retinoic acid induction of CD38 antigen expression on normal and leukemic human myeloid cells: relationship with cell differentiation. Leuk Lymphoma 44: 691–698.

51. HoutkooperRH, PirinenE, AuwerxJ (2012) Sirtuins as regulators of metabolism and healthspan. Nature Reviews Molecular Cell Biology 13: 225–238.

52. MorrisBJ (2013) Seven sirtuins for seven deadly diseases of aging. Free Radical Biology and Medicine 56: 133–171.

53. RothM, ChenWY (2013) Sorting out functions of sirtuins in cancer. Oncogene 33(13): 1609–20 doi:10.1038/onc.2013.120

54. YuanH, SuL, ChenWY (2013) The emerging and diverse roles of sirtuins in cancer: a clinical perspective. OncoTargets & Therapy 6: 1399–1416.

55. WangZ, ChenWY (2013) Emerging Roles of SIRT1 in Cancer Drug Resistance. Genes Cancer 4: 82–90.

56. LiL, WangL, WangZ, HoY, McDonaldT, et al. (2012) Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib. Cancer Cell 21: 266–281.

57. Bolton-GillespieE, SchemionekM, KleinHU, FlisS, HoserG, et al. (2013) Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells. Blood 121: 4175–4183.

58. DamleRN, WasilT, FaisF, GhiottoF, ValettoA, et al. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94: 1840–1847.

59. BergthorsdottirS, GallagherA, JainandunsingS, CockayneD, SuttonJ, et al. (2001) Signals that initiate somatic hypermutation of B cells in vitro. J Immunol 166: 2228–2234.

60. MichorF, HughesTP, IwasaY, BranfordS, ShahNP, et al. (2005) Dynamics of chronic myeloid leukaemia. Nature 435: 1267–1270.

61. DiazLAJr, WilliamsRT, WuJ, KindeI, HechtJR, et al. (2012) The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486: 537–540.

62. YeK, SchulzMH, LongQ, ApweilerR, NingZ (2009) Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25: 2865–2871.

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Genetika Reprodukčná medicína

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PLOS Genetics


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