Acute myeloid leukemia with mutated nucleophosmin (NPM1): Any hope for a targeted therapy?

Blood Reviews

Volumn 25, Issue 6, 2011, Pages 247-254

  Falini, Brunangelo ^a   Gionfriddo, Ilaria ^a   Cecchetti, Federica ^a   Ballanti, Stelvio ^a   Pettirossi, Valentina ^a   Martelli, Maria Paola ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Acute myeloid leukemia; Chaperone; NPM1 mutations; Nucleolus; Nucleophosmin; Targeted therapy

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ARSENIC TRIOXIDE; AZACITIDINE; CYTARABINE; FLAVOPIRIDOL; GEMTUZUMAB OZOGAMICIN; LENALIDOMIDE; LEPTOMYCIN B; MITOXANTRONE; MUTANT PROTEIN; NUCLEOPHOSMIN; RETINOIC ACID; ROSCOVITINE;

ACUTE GRANULOCYTIC LEUKEMIA; ANOREXIA; APOPTOSIS; ARTICLE; BONE MARROW TUMOR; CELL DIFFERENTIATION; CLINICAL FEATURE; CYTOPLASM; DRUG ACTIVITY; DRUG MEGADOSE; DRUG TARGETING; FOUNDER EFFECT; GENE MUTATION; HISTOPATHOLOGY; HUMAN; LEUKEMIA RELAPSE; LOW DRUG DOSE; MALAISE; MINIMAL RESIDUAL DISEASE; MOLECULARLY TARGETED THERAPY; MYELODYSPLASTIC SYNDROME; NONHUMAN; NUCLEOLUS; PRE EMPTIVE THERAPY; PRIORITY JOURNAL; PROMYELOCYTIC LEUKEMIA; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; QUANTITATIVE ANALYSIS; THERAPY; TUMOR CLASSIFICATION;

ANIMALS; ANTINEOPLASTIC AGENTS; EPIGENESIS, GENETIC; HUMANS; LEUKEMIA, MYELOID, ACUTE; MUTATION; NUCLEAR PROTEINS; PROTEIN TRANSPORT;

EID: 80055007688     PISSN: 0268960X     EISSN: 15321681     Source Type: Journal    
DOI: 10.1016/j.blre.2011.06.001     Document Type: Article

References (115)

1. Lowenberg B. Acute myeloid leukemia: the challenge of capturing disease variety. Hematology Am Soc Hematol Educ Program 2008, 2008:1-11.
2. Rowe J.M. Optimal induction and post-remission therapy for AML in first remission. Hematology Am Soc Hematol Educ Program 2009, 396-405.
3. Burnett A., Wetzler M., Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011, 29:487-494.
4. Sanz M.A., Grimwade D., Tallman M.S., Lowenberg B., Fenaux P., Estey E.H., et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2009, 113:1875-1891.
5. Falini B., Mecucci C., Tiacci E., Alcalay M., Rosati R., Pasqualucci L., et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005, 352:254-266.
6. Falini B., Martelli M.P., Tiacci E., Ascani S., Thiede C., Pileri S.A. Immunohistochemical surrogates for genetic alterations of CCDN1, PML, ALK, and NPM1 genes in lymphomas and acute myeloid leukemia. Best Pract Res Clin Haematol 2010, 23:417-431.
7. Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., et al. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 2008, 456:66-72.
8. Mardis E.R., Ding L., Dooling D.J., Larson D.E., McLellan M.D., Chen K., et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009, 361:1058-1066.
9. Ley T.J., Ding L., Walter M.J., McLellan M.D., Lamprecht T., Larson D.E., et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med 2010, 363:2424-2433.
10. Yan X.J., Xu J., Gu Z.H., Pan C.M., Lu G., Shen Y., et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011, 43:309-315.
11. Falini B., Nicoletti I., Martelli M.F., Mecucci C. Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. Blood 2007, 109:874-885.
12. Falini B., Sportoletti P., Martelli M.P. Acute myeloid leukemia with mutated NPM1: diagnosis, prognosis and therapeutic perspectives. Curr Opin Oncol 2009, 21:573-581.
13. Arber D., Brunning R.D., Le Beau M.M., Falini B., Vardiman J.W., Porwit A., et al. Acute myeloid leukaemia with recurrent genetic abnormalities. WHO classification of tumours of haematopoietic and lymphoid tissues 2008, 110-123. International Agency for Research on Cancer (IARC), Lyon, France. S.E. Swerdlow, E. Campo, N.L. Harris (Eds.).
14. Anderson K., Lutz C., van Delft F.W., Bateman C.M., Guo Y., Colman S.M., et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature 2011, 469:356-361.
15. Falini B., Martelli M.P., Bolli N., Sportoletti P., Liso A., Tiacci E., et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity?. Blood 2011, 117:1109-1120.
16. Liso A., Bogliolo A., Freschi V., Martelli M.P., Pileri S.A., Santodirocco M., et al. In human genome, generation of a nuclear export signal through duplication appears unique to nucleophosmin (NPM1) mutations and is restricted to AML. Leukemia 2008, 22:1285-1289.
17. Chou W.C., Tang J.L., Lin L.I., Yao M., Tsay W., Chen C.Y., et al. Nucleophosmin mutations in de novo acute myeloid leukemia: the age-dependent incidences and the stability during disease evolution. Cancer Res 2006, 66:3310-3316.
18. Falini B., Martelli M.P., Mecucci C., Liso A., Bolli N., Bigerna B., et al. Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice. Haematologica 2008, 93:775-779.
19. Falini B., Mecucci C., Saglio G., Lo Coco F., Diverio D., Brown P., et al. NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia. Haematologica 2008, 93:439-442.
20. Alcalay M., Tiacci E., Bergomas R., Bigerna B., Venturini E., Minardi S.P., et al. Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance. Blood 2005, 106:899-902.
21. Verhaak R.G., Goudswaard C.S., van Putten W., Bijl M.A., Sanders M.A., Hugens W., et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood 2005, 106:3747-3754.
22. Becker H., Marcucci G., Maharry K., Radmacher M.D., Mrozek K., Margeson D., et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. J Clin Oncol 2010, 28:596-604.
23. Garzon R., Garofalo M., Martelli M.P., Briesewitz R., Wang L., Fernandez-Cymering C., et al. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 2008, 105:3945-3950.
24. Jongen-Lavrencic M., Sun S.M., Dijkstra M.K., Valk P.J., Lowenberg B. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 2008, 111:5078-5085.
25. Martelli M.P., Pettirossi V., Thiede C., Bonifacio E., Mezzasoma F., Cecchini D., et al. CD34+ cells from AML with mutated NPM1 harbor cytoplasmic mutated nucleophosmin and generate leukemia in immunocompromised mice. Blood 2010, 116:3907-3922.
26. Taussig D.C., Vargaftig J., Miraki-Moud F., Griessinger E., Sharrock K., Luke T., et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction. Blood 2010, 115:1976-1984.
27. Shih L.Y., Huang C.F., Wu J.H., Lin T.L., Dunn P., Wang P.N., et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood 2002, 100:2387-2392.
28. Renneville A., Roumier C., Biggio V., Nibourel O., Boissel N., Fenaux P., et al. Cooperating gene mutations in acute myeloid leukemia: a review of the literature. Leukemia 2008, 22:915-931.
29. Bacher U., Haferlach T., Schoch C., Kern W., Schnittger S. Implications of NRAS mutations in AML: a study of 2502 patients. Blood 2006, 107:3847-3853.
30. Marcucci G., Maharry K., Wu Y.Z., Radmacher M.D., Mrozek K., Margeson D., et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 2010, 28:2348-2355.
31. Falini B., Bolli N., Liso A., Martelli M.P., Mannucci R., Pileri S., et al. Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications. Leukemia 2009, 23:1731-1743.
32. Cordell J.L., Pulford K.A., Bigerna B., Roncador G., Banham A., Colombo E., et al. Detection of normal and chimeric nucleophosmin in human cells. Blood 1999, 93:632-642.
33. Borer R.A., Lehner C.F., Eppenberger H.M., Nigg E.A. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell 1989, 56:379-390.
34. Yun J.P., Chew E.C., Liew C.T., Chan J.Y., Jin M.L., Ding M.X., et al. Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix. J Cell Biochem 2003, 90:1140-1148.
35. Grisendi S., Mecucci C., Falini B., Pandolfi P.P. Nucleophosmin and cancer. Nat Rev Cancer 2006, 6:493-505.
36. Hingorani K., Szebeni A., Olson M.O. Mapping the functional domains of nucleolar protein B23. J Biol Chem 2000, 275:24451-24457.
37. Bogerd H.P., Fridell R.A., Benson R.E., Hua J., Cullen B.R. Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay. Mol Cell Biol 1996, 16:4207-4214.
38. Wang W., Budhu A., Forgues M., Wang X.W. Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication. Nat Cell Biol 2005, 7:823-830.
39. Yu Y., Maggi L.B., Brady S.N., Apicelli A.J., Dai M.S., Lu H., et al. Nucleophosmin is essential for ribosomal protein L5 nuclear export. Mol Cell Biol 2006, 26:3798-3809.
40. Kau T.R., Way J.C., Silver P.A. Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer 2004, 4:106-117.
41. Kudo N., Matsumori N., Taoka H., Fujiwara D., Schreiner E.P., Wolff B., et al. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci U S A 1999, 96:9112-9117.
42. Dong X., Biswas A., Suel K.E., Jackson L.K., Martinez R., Gu H., et al. Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature 2009, 458:1136-1141.
43. Daelemans D., Costes S.V., Lockett S., Pavlakis G.N. Kinetic and molecular analysis of nuclear export factor CRM1 association with its cargo in vivo. Mol Cell Biol 2005, 25:728-739.
44. Misteli T. Physiological importance of RNA and protein mobility in the cell nucleus. Histochem Cell Biol 2008, 129:5-11.
45. Muro E., Hoang T.Q., Jobart-Malfait A., Hernandez-Verdun D. In nucleoli, the steady state of nucleolar proteins is leptomycin B-sensitive. Biol Cell 2008, 100:303-313.
46. Grummitt C.G., Townsley F.M., Johnson C.M., Warren A.J., Bycroft M. Structural consequences of nucleophosmin mutations in acute myeloid leukemia. J Biol Chem 2008, 283:23326-23332.
47. Emmott E., Hiscox J.A. Nucleolar targeting: the hub of the matter. EMBO Rep 2009, 10:231-238.
48. Wanzel M., Russ A.C., Kleine-Kohlbrecher D., Colombo E., Pelicci P.G., Eilers M. A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. Nat Cell Biol 2008, 10:1051-1061.
49. Falini B., Bolli N., Shan J., Martelli M.P., Liso A., Pucciarini A., et al. Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood 2006, 107:4514-4523.
50. Nakagawa M., Kameoka Y.R.S. Nucleophosmin in acute myelogenous leukemia (letter). N Engl J Med 2005, 352:1819-1820.
51. Bolli N., Nicoletti I., De Marco M.F., Bigerna B., Pucciarini A., Mannucci R., et al. Born to be exported: COOH-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants. Cancer Res 2007, 67:6230-6237.
52. Newlands E.S., Rustin G.J., Brampton M.H. Phase I trial of elactocin. Br J Cancer 1996, 74:648-649.
53. Mutka S.C., Yang W.Q., Dong S.D., Ward S.L., Craig D.A., Timmermans P.B., et al. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res 2009, 69:510-517.
54. Scaloni F., Federici L., Brunori M., Gianni S. Deciphering the folding transition state structure and denatured state properties of nucleophosmin C-terminal domain. Proc Natl Acad Sci U S A 2010, 107:5447-5452.
55. Bolli N., De Marco M.F., Martelli M.P., Bigerna B., Pucciarini A., Rossi R., et al. A dose-dependent tug of war involving the NPM1 leukaemic mutant, nucleophosmin, and ARF. Leukemia 2009, 23:501-509.
56. Grisendi S., Bernardi R., Rossi M., Cheng K., Khandker L., Manova K., et al. Role of nucleophosmin in embryonic development and tumorigenesis. Nature 2005, 437:147-153.
57. Ahmad Y., Boisvert F.M., Gregor P., Cobley A., Lamond A.I. NOPdb: nucleolar proteome database-2008 update. Nucleic Acids Res 2009, 37:D181-D184.
58. Dundr M., Misteli T., Olson M.O. The dynamics of postmitotic reassembly of the nucleolus. J Cell Biol 2000, 150:433-446.
59. Krasowski M.D., Reschly E.J., Ekins S. Intrinsic disorder in nuclear hormone receptors. J Proteome Res 2008, 7:4359-4372.
60. He X., Zhang J. Why do hubs tend to be essential in protein networks?. PLoS Genet 2006, 2:e88.
61. Wright P.E., Dyson H.J. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 1999, 293:321-331.
62. Gunasekaran K., Tsai C.J., Kumar S., Zanuy D., Nussinov R. Extended disordered proteins: targeting function with less scaffold. Trends Biochem Sci 2003, 28:81-85.
63. Amin M.A., Matsunaga S., Uchiyama S., Fukui K. Depletion of nucleophosmin leads to distortion of nucleolar and nuclear structures in HeLa cells. Biochem J 2008, 415:345-351.
64. Yun C., Wang Y., Mukhopadhyay D., Backlund P., Kolli N., Yergey A., et al. Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases. J Cell Biol 2008, 183:589-595.
65. Lindstrom M.S. Emerging functions of ribosomal proteins in gene-specific transcription and translation. Biochem Biophys Res Commun 2009, 379:167-170.
66. Chan P.K., Chan F.Y. A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin. Biochem Pharmacol 1999, 57:1265-1273.
67. Burger K., Muhl B., Harasim T., Rohrmoser M., Malamoussi A., Orban M., et al. Chemotherapeutic drugs inhibit ribosome biogenesis at various levels. J Biol Chem 2010, 285:12416-12425.
68. Rubbi C.P., Milner J. Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses. EMBO J 2003, 22:6068-6077.
69. Lowenberg B., Ossenkoppele G.J., van Putten W., Schouten H.C., Graux C., Ferrant A., et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009, 361:1235-1248.
70. Fernandez H.F., Sun Z., Yao X., Litzow M.R., Luger S.M., Paietta E.M., et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009, 361:1249-1259.
71. Perera Y., Farina H.G., Gil J., Rodriguez A., Benavent F., Castellanos L., et al. Anticancer peptide CIGB-300 binds to nucleophosmin/B23, impairs its CK2-mediated phosphorylation, and leads to apoptosis through its nucleolar disassembly activity. Mol Cancer Ther 2009, 8:1189-1196.
72. Jones P.A., Baylin S.B. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002, 3:415-428.
73. Shannon K., Armstrong S.A. Genetics, epigenetics, and leukemia. N Engl J Med 2010, 363:2460-2461.
74. Figueroa M.E., Lugthart S., Li Y., Erpelinck-Verschueren C., Deng X., Christos P.J., et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 2010, 17:13-27.
75. Jurkowska R.Z., Jurkowski T.P., Jeltsch A. Structure and function of mammalian DNA methyltransferases. Chembiochem 2011, 12:206-222.
76. Namboodiri V.M., Akey I.V., Schmidt-Zachmann M.S., Head J.F., Akey C.W. The structure and function of Xenopus NO38-core, a histone chaperone in the nucleolus. Structure 2004, 12:2149-2160.
77. Okuwaki M. The structure and functions of NPM1/Nucleophsmin/B23, a multifunctional nucleolar acidic protein. J Biochem 2008, 143:441-448.
78. Lindstrom M.S. NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011, 2011:195209.
79. Gadad S.S., Senapati P., Syed S.H., Rajan R.E., Shandilya J., Swaminathan V., et al. the multifunctional protein nucleophosmin (npm1) is a human linker histone h1 chaperone. Biochemistry 2011, 50:2780-2789.
80. Colombo E., Alcalay M., Pelicci P.G. Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases. Oncogene 2011, 30:2595-2609.
81. Okuwaki M., Matsumoto K., Tsujimoto M., Nagata K. Function of nucleophosmin/B23, a nucleolar acidic protein, as a histone chaperone. FEBS Lett 2001, 506:272-276.
82. Swaminathan V., Kishore A.H., Febitha K.K., Kundu T.K. Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription. Mol Cell Biol 2005, 25:7534-7545.
83. Schiffer C.A. Myelodysplasia: the good, the fair and the ugly. Best Pract Res Clin Haematol 2007, 20:49-55.
84. Erba H.P. Has there been progress in the treatment of older patients with acute myeloid leukemia?. Best Pract Res Clin Haematol 2010, 23:495-501.
85. Wermke M., Thiede C., Kiani A., Ehninger G., Bornhauser M., Platzbecker U. Successful treatment of molecular relapse in NPM1-positive AML using 5-azacytidine. Leukemia 2010, 24:236-237.
86. Ayala F., Dewar R., Kieran M., Kalluri R. Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia 2009, 23:2233-2241.
87. Quentmeier H., Martelli M.P., Dirks W.G., Bolli N., Liso A., Macleod R.A., et al. Cell line OCI/AML3 bears exon-12 NPM gene mutation-A and cytoplasmic expression of nucleophosmin. Leukemia 2005, 19:1760-1767.
88. Hatfield K.J., Hovland R., Oyan A.M., Kalland K.H., Ryningen A., Gjertsen B.T., et al. Release of angiopoietin-1 by primary human acute myelogenous leukemia cells is associated with mutations of nucleophosmin, increased by bone marrow stromal cells and possibly antagonized by high systemic angiopoietin-2 levels. Leukemia 2008, 22:287-293.
89. Padron E., Komrokji R., List A.F. Biology and treatment of the 5q- syndrome. Expert Rev Hematol 2011, 4:61-69.
90. Framson P.E., Sage E.H. SPARC and tumor growth: where the seed meets the soil?. J Cell Biochem 2004, 92:679-690.
91. Pellagatti A., Jadersten M., Forsblom A.M., Cattan H., Christensson B., Emanuelsson E.K., et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients. Proc Natl Acad Sci U S A 2007, 104:11406-11411.
92. Fehniger T.A., Uy G.L., Trinkaus K., Nelson A.D., Demland J., Abboud C.N., et al. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood 2011, 117:1828-1833.
93. Shao H.Y., Miao Z.Y., Hui C., Qin F.X., Chen X.C., Tan S., et al. Nucleophosmin gene mutations promote NIH3T3 cell migration and invasion through CXCR4 and MMPs. Exp Mol Pathol 2011, 90:38-44.
94. Oelschlaegel U., Mohr B., Schaich M., Schakel U., Kroschinsky F., Illmer T., et al. HLA-DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemia. Cytometry B Clin Cytom 2009, 76:321-327.
95. Burger J.A., Peled A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 2009, 23:43-52.
96. De Propriis M.S., Raponi S., Diverio D., Milani M.L., Meloni G., Falini B., et al. High CD33 expression levels in acute myeloid leukemia cells carrying the nucleophosmin (NPM1) mutation. Haematologica 2011, 96:1548-1551.
97. Chevallier P., Prebet T., Pigneux A., Hunault M., Delaunay J., Perry F., et al. Influence of NPM1 and FLT3-ITD status on outcome in relapsed/refractory AML patients receiving salvage therapy including gemtuzumab ozogamicin. Leukemia 2010, 24:467-469.
98. Schlenk R.F., Dohner K., Kneba M., Gotze K., Hartmann F., Del Valle F., et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica 2009, 94:54-60.
99. Burnett A.K., Hills R.K., Green C., Jenkinson S., Koo K., Patel Y., et al. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood 2010, 115:948-956.
100. Liu H., Tan B.C., Tseng K.H., Chuang C.P., Yeh C.W., Chen K.D., et al. Nucleophosmin acts as a novel AP2alpha-binding transcriptional corepressor during cell differentiation. EMBO Rep 2007, 8:394-400.
101. Dohner H. Implication of the molecular characterization of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2007, 412-419.
102. Martelli M.P., Pettirossi V., Manes N., Liso A., Mezzasoma F., Cecchetti F., et al. Selective silencing of the NPM1 mutant protein and apoptosis induction upon ATRA in vitro treatment of AML cells carrying NPM1 mutations. Blood (ASH Annual Meeting Abstracts) 2007, 110:868.
103. Karp J.E., Smith B.D., Levis M.J., Gore S.D., Greer J., Hattenburg C., et al. Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemia. Clin Cancer Res 2007, 13:4467-4473.
104. Karp J.E., Smith B.D., Resar L.S., Greer J.M., Blackford A., Zhao M., et al. Phase I and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood 2011, 117:3302-3310.
105. Gurumurthy M., Tan C.H., Ng R., Zeiger L., Lau J., Lee J., et al. Nucleophosmin interacts with HEXIM1 and regulates RNA polymerase II transcription. J Mol Biol 2008, 378:302-317.
106. Schnittger S., Kern W., Tschulik C., Weiss T., Dicker F., Falini B., et al. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 2009, 114:2220-2231.
107. Gorello P., Cazzaniga G., Alberti F., Dell'Oro M.G., Gottardi E., Specchia G., et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 2006, 20:1103-1108.
108. Hokland P., Ommen H.B. Towards individualized follow-up in adult acute myeloid leukemia in remission. Blood 2011, 117:2577-2584.
109. Liso A., Colau D., Benmaamar R., De Groot A., Martin W., Benedetti R., et al. Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules. Leukemia 2008, 22:424-426.
110. Chi H.T., Vu H.A., Iwasaki R., Nagamura F., Tojo A., Watanabe T., et al. Detection of exon 12 type A mutation of NPM1 gene in IMS-M2 cell line. Leuk Res 2010, 34:261-262.
111. Wang C., Curtis J.E., Minden M.D., McCulloch E.A. Expression of a retinoic acid receptor gene in myeloid leukemia cells. Leukemia 1989, 3:264-269.
112. Stratton M.R., Campbell P.J., Futreal P.A. The cancer genome. Nature 2009, 458:719-724.
113. Vassiliou G.S., Cooper J.L., Rad R., Li J., Rice S., Uren A., et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat Genet 2011, 43:470-475.
114. Cheng K., Sportoletti P., Ito K., Clohessy J.G., Teruya-Feldstein J., Kutok J.L., et al. The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model. Blood 2010, 115:3341-3345.
115. Bolli N., Payne E.M., Grabher C., Lee J.S., Johnston A.B., Falini B., et al. Expression of the cytoplasmic NPM1 mutant (NPMc+) causes the expansion of hematopoietic cells in zebrafish. Blood 2010, 115:3329-3340.