Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype

doi:10.1056/NEJMoa041974

A correction has been published: N Engl J Med 2005;352(7):740.

Volume 352:254-266		January 20, 2005		Number 3

Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype

Brunangelo Falini, M.D., Cristina Mecucci, M.D., Ph.D., Enrico Tiacci, M.D., Myriam Alcalay, M.D., Ph.D., Roberto Rosati, Ph.D., Laura Pasqualucci, M.D., Roberta La Starza, M.D., Ph.D., Daniela Diverio, M.D., Emanuela Colombo, Ph.D., Antonella Santucci, M.D., Barbara Bigerna, Roberta Pacini, Alessandra Pucciarini, Ph.D., Arcangelo Liso, M.D., Marco Vignetti, M.D., Paola Fazi, M.D., Natalia Meani, Ph.D., Valentina Pettirossi, Ph.D., Giuseppe Saglio, M.D., Franco Mandelli, M.D., Francesco Lo-Coco, M.D., Pier-Giuseppe Pelicci, M.D., Ph.D., Massimo F. Martelli, M.D., for the GIMEMA Acute Leukemia Working Party

Full Text

PDF

PDA Full Text

PowerPoint Slide Set

Supplementary Material

Editorial
by Grisendi, S.

Letters

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

E-mail When Letters Appear

Related Article

PubMed Citation

ABSTRACT

Background Nucleophosmin (NPM), a nucleocytoplasmic shuttlingprotein with prominent nucleolar localization, regulates theARF-p53 tumor-suppressor pathway. Translocations involving theNPM gene cause cytoplasmic dislocation of the NPM protein.

Methods We used immunohistochemical methods to study the subcellularlocalization of NPM in bone marrow–biopsy specimens from591 patients with primary acute myelogenous leukemia (AML).We then correlated the presence of cytoplasmic NPM with clinicaland biologic features of the disease.

Results Cytoplasmic NPM was detected in 208 (35.2 percent) ofthe 591 specimens from patients with primary AML but not in135 secondary AML specimens or in 980 hematopoietic or extrahematopoieticneoplasms other than AML. It was associated with a wide spectrumof morphologic subtypes of the disease, a normal karyotype,and responsiveness to induction chemotherapy, but not with recurrentgenetic abnormalities. There was a high frequency of FLT3 internaltandem duplications and absence of CD34 and CD133 in AML specimenswith a normal karyotype and cytoplasmic dislocation of NPM,but not in those in which the protein was restricted to thenucleus. AML specimens with cytoplasmic NPM carried mutationsof the NPM gene that were predicted to alter the protein atits C-terminal; this mutant gene caused cytoplasmic localizationof NPM in transfected cells.

Conclusions Cytoplasmic NPM is a characteristic feature of alarge subgroup of patients with AML who have a normal karyotype,NPM gene mutations, and responsiveness to induction chemotherapy.

Source Information

From the Institute of Hematology (B.F., C.M., E.T., R.R., L.P., R.L.S., A.S., B.B., R.P., A.P., M.F.M.) and the Department of Biochemistry and Molecular Biotechnology (V.P.), University of Perugia, Perugia, Italy; the European Institute of Oncology, Milan, Italy (M.A., E.C., N.M., P.-G.P.); the Institute for Cancer Genetics, Columbia University, New York (L.P.); the Institute of Hematology, University La Sapienza, Rome (D.D., F.M.); the Institute of Hematology, University of Foggia, Foggia, Italy (A.L.); the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Data Center, Rome (M.V., P.F.); the Division of Internal Medicine and Hematology, Ospedale S. Luigi, Orbassano-Turin, Italy (G.S.); and the Department of Biopathology, University of Tor Vergata, Rome (F.L.-C.).

Drs. Tiacci, Alcalay, and Rosati contributed equally to this article.

Address reprint requests to Dr. Falini at the Institute of Hematology, Policlinico Monteluce, 06122 Perugia, Italy, or at faliniem{at}unipg.it.

Full Text of this Article

Related Letters:

Nucleophosmin in Acute Myelogenous Leukemia
Nakagawa M., Kameoka Y., Suzuki R., Falini B., Mecucci C., Martelli M. F.
Extract | Full Text | PDF
N Engl J Med 2005; 352:1819-1820, Apr 28, 2005. Correspondence

This article has been cited by other articles:

Tanikawa, C., Ueda, K., Nakagawa, H., Yoshida, N., Nakamura, Y., Matsuda, K. (2009). Regulation of Protein Citrullination through p53/PADI4 Network in DNA Damage Response. Cancer Res. 69: 8761-8769 [Abstract] [Full Text]
Haferlach, C., Vignetti, M., Haferlach, T., Falini, B. (2009). Response: NPM1-mutated AML is an entity irrespective of whether or not chromosomal aberrations are present. Blood 114: 4602-4603 [Full Text]
Heuser, M., Sly, L. M., Argiropoulos, B., Kuchenbauer, F., Lai, C., Weng, A., Leung, M., Lin, G., Brookes, C., Fung, S., Valk, P. J., Delwel, R., Lowenberg, B., Krystal, G., Humphries, R. K. (2009). Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal. Blood 114: 3983-3993 [Abstract] [Full Text]
Cilloni, D., Renneville, A., Hermitte, F., Hills, R. K., Daly, S., Jovanovic, J. V., Gottardi, E., Fava, M., Schnittger, S., Weiss, T., Izzo, B., Nomdedeu, J., van der Heijden, A., van der Reijden, B. A., Jansen, J. H., van der Velden, V. H.J., Ommen, H., Preudhomme, C., Saglio, G., Grimwade, D. (2009). Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study. JCO 27: 5195-5201 [Abstract] [Full Text]
Silva, F. P.G., Almeida, I., Morolli, B., Brouwer-Mandema, G., Wessels, H., Vossen, R., Vrieling, H., Marijt, E. W.A., Valk, P. J.M., Kluin-Nelemans, H. C., Sperr, W. R., Ludwig, W.-D., Giphart-Gassler, M. (2009). Genome wide molecular analysis of minimally differentiated acute myeloid leukemia. haematol 94: 1546-1554 [Abstract] [Full Text]
Inder, K. L., Lau, C., Loo, D., Chaudhary, N., Goodall, A., Martin, S., Jones, A., van der Hoeven, D., Parton, R. G., Hill, M. M., Hancock, J. F. (2009). Nucleophosmin and Nucleolin Regulate K-Ras Plasma Membrane Interactions and MAPK Signal Transduction. J. Biol. Chem. 284: 28410-28419 [Abstract] [Full Text]
Haferlach, C., Mecucci, C., Schnittger, S., Kohlmann, A., Mancini, M., Cuneo, A., Testoni, N., Rege-Cambrin, G., Santucci, A., Vignetti, M., Fazi, P., Martelli, M. P., Haferlach, T., Falini, B. (2009). AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 114: 3024-3032 [Abstract] [Full Text]
Dey, B. R., Spitzer, T. R., Hasserjian, R. P. (2009). Case 28-2009 -- A 68-Year-Old Man with Fatigue, Cough, and Peripheral-Blood Monocytosis. NEJM 361: 1099-1106 [Full Text]
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., Fulton, L. A., Locke, D. P., Magrini, V. J., Abbott, R. M., Vickery, T. L., Reed, J. S., Robinson, J. S., Wylie, T., Smith, S. M., Carmichael, L., Eldred, J. M., Harris, C. C., Walker, J., Peck, J. B., Du, F., Dukes, A. F., Sanderson, G. E., Brummett, A. M., Clark, E., McMichael, J. F., Meyer, R. J., Schindler, J. K., Pohl, C. S., Wallis, J. W., Shi, X., Lin, L., Schmidt, H., Tang, Y., Haipek, C., Wiechert, M. E., Ivy, J. V., Kalicki, J., Elliott, G., Ries, R. E., Payton, J. E., Westervelt, P., Tomasson, M. H., Watson, M. A., Baty, J., Heath, S., Shannon, W. D., Nagarajan, R., Link, D. C., Walter, M. J., Graubert, T. A., DiPersio, J. F., Wilson, R. K., Ley, T. J. (2009). Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome. NEJM 361: 1058-1066 [Abstract] [Full Text]
Schnittger, S., Kern, W., Tschulik, C., Weiss, T., Dicker, F., Falini, B., Haferlach, C., Haferlach, T. (2009). Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 114: 2220-2231 [Abstract] [Full Text]
Campidelli, C., Agostinelli, C., Stitson, R., Pileri, S. A. (2009). Myeloid Sarcoma: Extramedullary Manifestation of Myeloid Disorders. Am J Clin Pathol 132: 426-437 [Abstract] [Full Text]
Nawa, Y., Kawahara, K.-i., Tancharoen, S., Meng, X., Sameshima, H., Ito, T., Masuda, Y., Imaizumi, H., Hashiguchi, T., Maruyama, I. (2009). Nucleophosmin may act as an alarmin: implications for severe sepsis. J. Leukoc. Biol. 86: 645-653 [Abstract] [Full Text]
Scaloni, F., Gianni, S., Federici, L., Falini, B., Brunori, M. (2009). Folding mechanism of the C-terminal domain of nucleophosmin: residual structure in the denatured state and its pathophysiological significance. FASEB J. 23: 2360-2365 [Abstract] [Full Text]
Vardiman, J. W., Thiele, J., Arber, D. A., Brunning, R. D., Borowitz, M. J., Porwit, A., Harris, N. L., Le Beau, M. M., Hellstrom-Lindberg, E., Tefferi, A., Bloomfield, C. D. (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114: 937-951 [Abstract] [Full Text]
Ho, P. A., Alonzo, T. A., Gerbing, R. B., Pollard, J., Stirewalt, D. L., Hurwitz, C., Heerema, N. A., Hirsch, B., Raimondi, S. C., Lange, B., Franklin, J. L., Radich, J. P., Meshinchi, S. (2009). Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 113: 6558-6566 [Abstract] [Full Text]
De Preter, K., De Brouwer, S., Van Maerken, T., Pattyn, F., Schramm, A., Eggert, A., Vandesompele, J., Speleman, F. (2009). Meta-mining of Neuroblastoma and Neuroblast Gene Expression Profiles Reveals Candidate Therapeutic Compounds. Clin. Cancer Res. 15: 3690-3696 [Abstract] [Full Text]
Bacher, U., Kohlmann, A., Haferlach, T. (2009). Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies. Brief Funct Genomic Proteomic 0: elp011v1-elp011 [Abstract] [Full Text]
Schneider, F., Hoster, E., Unterhalt, M., Schneider, S., Dufour, A., Benthaus, T., Mellert, G., Zellmeier, E., Bohlander, S. K., Feuring-Buske, M., Buske, C., Braess, J., Fritsch, S., Heinecke, A., Sauerland, M. C., Berdel, W. E., Buechner, T., Woermann, B. J., Hiddemann, W., Spiekermann, K. (2009). NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS). Blood 113: 5250-5253 [Abstract] [Full Text]
Cui, Y.-X., Kerby, A., McDuff, F. K. E., Ye, H., Turner, S. D. (2009). NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner. Blood 113: 5217-5227 [Abstract] [Full Text]
Klepin, H. D., Balducci, L. (2009). Acute Myelogenous Leukemia in Older Adults. The Oncologist 14: 222-232 [Abstract] [Full Text]
Cullen, S. P., Afonina, I. S., Donadini, R., Luthi, A. U., Medema, J. P., Bird, P. I., Martin, S. J. (2009). Nucleophosmin Is Cleaved and Inactivated by the Cytotoxic Granule Protease Granzyme M during Natural Killer Cell-mediated Killing. J. Biol. Chem. 284: 5137-5147 [Abstract] [Full Text]
Facchetti, F., Pileri, S. A., Agostinelli, C., Martelli, M. P., Paulli, M., Venditti, A., Martelli, M. F, Falini, B. (2009). Cytoplasmic nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm. haematol 94: 285-288 [Abstract] [Full Text]
Meloni, G., Mancini, M., Gianfelici, V., Martelli, M. P., Foa, R., Falini, B. (2009). Late relapse of acute myeloid leukemia with mutated NPM1 after eight years: evidence of NPM1 mutation stability. haematol 94: 298-300 [Full Text]
Akagi, T., Ogawa, S., Dugas, M., Kawamata, N., Yamamoto, G., Nannya, Y., Sanada, M., Miller, C. W., Yung, A., Schnittger, S., Haferlach, T., Haferlach, C., Koeffler, H. P. (2009). Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype. haematol 94: 213-223 [Abstract] [Full Text]
Buchner, T., Berdel, W. E., Haferlach, C., Haferlach, T., Schnittger, S., Muller-Tidow, C., Braess, J., Spiekermann, K., Kienast, J., Staib, P., Gruneisen, A., Kern, W., Reichle, A., Maschmeyer, G., Aul, C., Lengfelder, E., Sauerland, M.-C., Heinecke, A., Wormann, B., Hiddemann, W. (2009). Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group. JCO 27: 61-69 [Abstract] [Full Text]
Verhaak, R. G.W., Wouters, B. J., Erpelinck, C. A.J., Abbas, S., Beverloo, H. B., Lugthart, S., Lowenberg, B., Delwel, R., Valk, P. J.M. (2009). Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling. haematol 94: 131-134 [Abstract] [Full Text]
Morra, E., Barosi, G., Bosi, A., Ferrara, F., Locatelli, F., Marchetti, M., Martinelli, G., Mecucci, C., Vignetti, M., Tura, S. (2009). Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. haematol 94: 102-112 [Abstract] [Full Text]
Martelli, M. P., Pettirossi, V., Bonifacio, E., Mezzasoma, F., Manes, N., Cecchini, D., Capanni, M., Gionfriddo, I., Liso, A., Pacini, R., Carini, M., Specchia, G., Martelli, M. F, Falini, B. (2008). Evidence for CD34+ Hematopoietic Progenitor Cell Involvement in Acute Myeloid Leukemia with NPM1 Gene Mutation: Implications for the Cell of Origin. ASH ANNUAL MEETING ABSTRACTS 112: 307-307 [Abstract] [Full Text]
Metzeler, K. H., Hummel, M., Bloomfield, C. D., Spiekermann, K., Braess, J., Sauerland, M.-C., Heinecke, A., Radmacher, M., Marcucci, G., Whitman, S. P., Maharry, K., Paschka, P., Larson, R. A., Berdel, W. E., Buchner, T., Wormann, B., Mansmann, U., Hiddemann, W., Bohlander, S. K., Buske, C., for Cancer and Leukemia Group B and the German AML, (2008). An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood 112: 4193-4201 [Abstract] [Full Text]
Marcucci, G., Maharry, K., Radmacher, M. D., Mrozek, K., Vukosavljevic, T., Paschka, P., Whitman, S. P., Langer, C., Baldus, C. D., Liu, C.-G., Ruppert, A. S., Powell, B. L., Carroll, A. J., Caligiuri, M. A., Kolitz, J. E., Larson, R. A., Bloomfield, C. D. (2008). Prognostic Significance of, and Gene and MicroRNA Expression Signatures Associated With, CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia With High-Risk Molecular Features: A Cancer and Leukemia Group B Study. JCO 26: 5078-5087 [Abstract] [Full Text]
Di Fiore, P. P. (2008). Playing both sides: nucleophosmin between tumor suppression and oncogenesis. JCB 182: 7-9 [Abstract] [Full Text]
Bonetti, P., Davoli, T., Sironi, C., Amati, B., Pelicci, P. G., Colombo, E. (2008). Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7{gamma}. JCB 182: 19-26 [Abstract] [Full Text]
Paschka, P., Marcucci, G., Ruppert, A. S., Whitman, S. P., Mrozek, K., Maharry, K., Langer, C., Baldus, C. D., Zhao, W., Powell, B. L., Baer, M. R., Carroll, A. J., Caligiuri, M. A., Kolitz, J. E., Larson, R. A., Bloomfield, C. D. (2008). Wilms' Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. JCO 26: 4595-4602 [Abstract] [Full Text]
Radich, J. P. (2008). Molecular Classification of Acute Myeloid Leukemia: Are We There Yet?. JCO 26: 4539-4541 [Full Text]
Boonthimat, C., Thongnoppakhun, W., Auewarakul, C. U. (2008). Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations. haematol 93: 1565-1569 [Abstract] [Full Text]
Zimmerman, R. S., Rosenberg, N. (2008). Changes in p19Arf Localization Accompany Apoptotic Crisis during Pre-B-Cell Transformation by Abelson Murine Leukemia Virus. J. Virol. 82: 8383-8391 [Abstract] [Full Text]
Grummitt, C. G., Townsley, F. M., Johnson, C. M., Warren, A. J., Bycroft, M. (2008). Structural Consequences of Nucleophosmin Mutations in Acute Myeloid Leukemia. J. Biol. Chem. 283: 23326-23332 [Abstract] [Full Text]
Liso, A., Castiglione, F., Cappuccio, A., Stracci, F., Schlenk, R. F., Amadori, S., Thiede, C., Schnittger, S., Valk, P. J.M., Dohner, K., Martelli, M. F., Schaich, M., Krauter, J., Ganser, A., Martelli, M. P., Bolli, N., Lowenberg, B., Haferlach, T., Ehninger, G., Mandelli, F., Dohner, H., Michor, F., Falini, B. (2008). A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1). haematol 93: 1219-1226 [Abstract] [Full Text]
Dohner, K., Dohner, H. (2008). Molecular characterization of acute myeloid leukemia. haematol 93: 976-982 [Full Text]
Laughlin, T. S., Becker, M. W., Liesveld, J. L., Mulford, D. A., Abboud, C. N., Brown, P., Rothberg, P. G. (2008). Rapid Method for Detection of Mutations in the Nucleophosmin Gene in Acute Myeloid Leukemia. J. Mol. Diagn. 10: 338-345 [Abstract] [Full Text]
Pulsoni, A., Iacobelli, S., Bernardi, M., Borgia, M., Camera, A., Cantore, N., Di Raimondo, F., Fazi, P., Ferrara, F., Leoni, F., Liso, V., Mancini, M., Marmont, F., Matturro, A., Maurillo, L., Melillo, L., Meloni, G., Mirto, S., Specchia, G., Valentini, C. G., Venditti, A., Leone, G., Foa, R., Mandelli, F., Pagano, L. (2008). M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience. haematol 93: 1025-1032 [Abstract] [Full Text]
Lo-Coco, F., Cuneo, A., Pane, F., Cilloni, D., Diverio, D., Mancini, M., Testoni, N., Bardi, A., Izzo, B., Bolli, N., La Starza, R., Fazi, P., Iacobelli, S., Piciocchi, A., Vignetti, M., Amadori, S., Mandelli, F., Pelicci, P. G., Mecucci, C., Falini, B., Saglio, G., for the Acute Leukemia Working Party of the GIMEMA, (2008). Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia. haematol 93: 1017-1024 [Abstract] [Full Text]
Lindstrom, M. S., Zhang, Y. (2008). Ribosomal Protein S9 Is a Novel B23/NPM-binding Protein Required for Normal Cell Proliferation. J. Biol. Chem. 283: 15568-15576 [Abstract] [Full Text]
Langer, C., Radmacher, M. D., Ruppert, A. S., Whitman, S. P., Paschka, P., Mrozek, K., Baldus, C. D., Vukosavljevic, T., Liu, C.-G., Ross, M. E., Powell, B. L., de la Chapelle, A., Kolitz, J. E., Larson, R. A., Marcucci, G., Bloomfield, C. D. (2008). High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood 111: 5371-5379 [Abstract] [Full Text]
Schlenk, R. F., Dohner, K., Krauter, J., Frohling, S., Corbacioglu, A., Bullinger, L., Habdank, M., Spath, D., Morgan, M., Benner, A., Schlegelberger, B., Heil, G., Ganser, A., Dohner, H., the German-Austrian Acute Myeloid Leukemia Study, (2008). Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia. NEJM 358: 1909-1918 [Abstract] [Full Text]
Ottone, T., Ammatuna, E., Lavorgna, S., Noguera, N. I., Buccisano, F., Venditti, A., Gianni, L., Postorino, M., Federici, G., Amadori, S., Lo-Coco, F. (2008). An Allele-Specific RT-PCR Assay to Detect Type A Mutation of the Nucleophosmin-1 Gene in Acute Myeloid Leukemia. J. Mol. Diagn. 10: 212-216 [Abstract] [Full Text]
Wertheim, G., Bagg, A. (2008). Nucleophosmin (NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies. J. Mol. Diagn. 10: 198-202 [Abstract] [Full Text]
Szankasi, P., Jama, M., Bahler, D. W. (2008). A New DNA-Based Test for Detection of Nucleophosmin Exon 12 Mutations by Capillary Electrophoresis. J. Mol. Diagn. 10: 236-241 [Abstract] [Full Text]
Falini, B., Martelli, M. P., Mecucci, C., Liso, A., Bolli, N., Bigerna, B., Pucciarini, A., Pileri, S., Meloni, G., Martelli, M. F., Haferlach, T., Schnittger, S. (2008). Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice. haematol 93: 775-779 [Abstract] [Full Text]
Sportoletti, P., Grisendi, S., Majid, S. M., Cheng, K., Clohessy, J. G., Viale, A., Teruya-Feldstein, J., Pandolfi, P. P. (2008). Npm1 is a haploinsufficient suppressor of myeloid and lymphoid malignancies in the mouse. Blood 111: 3859-3862 [Abstract] [Full Text]
Garzon, R., Garofalo, M., Martelli, M. P., Briesewitz, R., Wang, L., Fernandez-Cymering, C., Volinia, S., Liu, C.-G., Schnittger, S., Haferlach, T., Liso, A., Diverio, D., Mancini, M., Meloni, G., Foa, R., Martelli, M. F., Mecucci, C., Croce, C. M., Falini, B. (2008). Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc. Natl. Acad. Sci. USA 105: 3945-3950 [Abstract] [Full Text]
Falini, B., Mecucci, C., Saglio, G., Coco, F. L., Diverio, D., Brown, P., Pane, F., Mancini, M., Martelli, M. P., Pileri, S., Haferlach, T., Haferlach, C., Schnittger, S. (2008). NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia. haematol 93: 439-442 [Abstract] [Full Text]
Bacher, U., Haferlach, C., Kern, W., Haferlach, T., Schnittger, S. (2008). Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients. Blood 111: 2527-2537 [Abstract] [Full Text]
Wandt, H., Schakel, U., Kroschinsky, F., Prange-Krex, G., Mohr, B., Thiede, C., Pascheberg, U., Soucek, S., Schaich, M., Ehninger, G. (2008). MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients. Blood 111: 1855-1861 [Abstract] [Full Text]
Yoneda-Kato, N., Kato, J.-y. (2008). Shuttling Imbalance of MLF1 Results in p53 Instability and Increases Susceptibility to Oncogenic Transformation. Mol. Cell. Biol. 28: 422-434 [Abstract] [Full Text]
Haferlach, T. (2008). Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia. ASH Education Book 2008: 400-411 [Abstract] [Full Text]
Stone, R. M. (2008). Genetically Defined Prognostic Factors and Novel Therapeutics for AML. Am Soc Clin Oncol Ed Book 2008: 280-284 [Abstract] [Full Text]
Kaspers, G. J.L., Zwaan, C. M. (2007). Pediatric acute myeloid leukemia: towards high-quality cure of all patients. haematol 92: 1519-1532 [Abstract] [Full Text]
Galietta, A., Gunby, R. H., Redaelli, S., Stano, P., Carniti, C., Bachi, A., Tucker, P. W., Tartari, C. J., Huang, C.-J., Colombo, E., Pulford, K., Puttini, M., Piazza, R. G., Ruchatz, H., Villa, A., Donella-Deana, A., Marin, O., Perrotti, D., Gambacorti-Passerini, C. (2007). NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma. Blood 110: 2600-2609 [Abstract] [Full Text]
Palmisano, M., Grafone, T., Ottaviani, E., Testoni, N., Baccarani, M., Martinelli, G. (2007). NPM1 mutations are more stable than FLT3 mutations during the course of disease in patients with acute myeloid leukemia. haematol 92: 1268-1269 [Abstract] [Full Text]
Ganapathi, K. A., Austin, K. M., Lee, C.-S., Dias, A., Malsch, M. M., Reed, R., Shimamura, A. (2007). The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 110: 1458-1465 [Abstract] [Full Text]
Link, D. C., Kunter, G., Kasai, Y., Zhao, Y., Miner, T., McLellan, M. D., Ries, R. E., Kapur, D., Nagarajan, R., Dale, D. C., Bolyard, A. A., Boxer, L. A., Welte, K., Zeidler, C., Donadieu, J., Bellanne-Chantelot, C., Vardiman, J. W., Caligiuri, M. A., Bloomfield, C. D., DiPersio, J. F., Tomasson, M. H., Graubert, T. A., Westervelt, P., Watson, M., Shannon, W., Baty, J., Mardis, E. R., Wilson, R. K., Ley, T. J. (2007). Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia. Blood 110: 1648-1655 [Abstract] [Full Text]
Brown, P., McIntyre, E., Rau, R., Meshinchi, S., Lacayo, N., Dahl, G., Alonzo, T. A., Chang, M., Arceci, R. J., Small, D. (2007). The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 110: 979-985 [Abstract] [Full Text]
Bolli, N., Nicoletti, I., De Marco, M. F., Bigerna, B., Pucciarini, A., Mannucci, R., Martelli, M. P., Liso, A., Mecucci, C., Fabbiano, F., Martelli, M. F., Henderson, B. R., Falini, B. (2007). Born to Be Exported: COOH-Terminal Nuclear Export Signals of Different Strength Ensure Cytoplasmic Accumulation of Nucleophosmin Leukemic Mutants. Cancer Res. 67: 6230-6237 [Abstract] [Full Text]
Liu, X., Liu, Z., Jang, S.-W., Ma, Z., Shinmura, K., Kang, S., Dong, S., Chen, J., Fukasawa, K., Ye, K. (2007). Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival. Proc. Natl. Acad. Sci. USA 104: 9679-9684 [Abstract] [Full Text]
Volpe, G., Cignetti, A., Panuzzo, C., Kuka, M., Vitaggio, K., Brancaccio, M., Perrone, G., Rinaldi, M., Prato, G., Fava, M., Geuna, M., Pautasso, M., Casnici, C., Signori, E., Tonon, G., Tarone, G., Marelli, O., Fazio, V. M., Saglio, G. (2007). Alternative BCR/ABL Splice Variants in Philadelphia Chromosome-Positive Leukemias Result in Novel Tumor-Specific Fusion Proteins that May Represent Potential Targets for Immunotherapy Approaches. Cancer Res. 67: 5300-5307 [Abstract] [Full Text]
Steensma, D. P. (2007). The spectrum of molecular aberrations in myelodysplastic syndromes: in the shadow of acute myeloid leukemia. haematol 92: 723-727 [Full Text]
Bacher, U., Haferlach, T., Kern, W., Haferlach, C., Schnittger, S. (2007). A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. haematol 92: 744-752 [Abstract] [Full Text]
Li, J., Sejas, D. P., Burma, S., Chen, D. J., Pang, Q. (2007). Nucleophosmin suppresses oncogene-induced apoptosis and senescence and enhances oncogenic cooperation in cells with genomic instability. Carcinogenesis 28: 1163-1170 [Abstract] [Full Text]
Falini, B., Nicoletti, I., Bolli, N., Martelli, M. P., Liso, A., Gorello, P., Mandelli, F., Mecucci, C., Martelli, M. F. (2007). Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias. haematol 92: 519-532 [Abstract] [Full Text]
Meshinchi, S., Arceci, R. J. (2007). Prognostic Factors and Risk-Based Therapy in Pediatric Acute Myeloid Leukemia. The Oncologist 12: 341-355 [Abstract] [Full Text]
Falini, B., Nicoletti, I., Martelli, M. F., Mecucci, C. (2007). Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features. Blood 109: 874-885 [Abstract] [Full Text]
Lechertier, T., Sirri, V., Hernandez-Verdun, D., Roussel, P. (2007). A B23-interacting sequence as a tool to visualize protein interactions in a cellular context. J. Cell Sci. 120: 265-275 [Abstract] [Full Text]
Mrozek, K., Marcucci, G., Paschka, P., Whitman, S. P., Bloomfield, C. D. (2007). Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?. Blood 109: 431-448 [Abstract] [Full Text]
Testa, U., Riccioni, R. (2007). Deregulation of apoptosis in acute myeloid leukemia. haematol 92: 81-94 [Abstract] [Full Text]
Suh, K. S., Crutchley, J. M., Koochek, A., Ryscavage, A., Bhat, K., Tanaka, T., Oshima, A., Fitzgerald, P., Yuspa, S. H. (2007). Reciprocal Modifications of CLIC4 in Tumor Epithelium and Stroma Mark Malignant Progression of Multiple Human Cancers. Clin. Cancer Res. 13: 121-131 [Abstract] [Full Text]
Pedersen-Bjergaard, J., Andersen, M. T., Andersen, M. K. (2007). Genetic Pathways in the Pathogenesis of Therapy-Related Myelodysplasia and Acute Myeloid Leukemia. ASH Education Book 2007: 392-397 [Abstract] [Full Text]
Dohner, H. (2007). Implication of the Molecular Characterization of Acute Myeloid Leukemia. ASH Education Book 2007: 412-419 [Abstract] [Full Text]
Grimwade, D. (2006). NPM1 mutation in AML: WHO and why?. Blood 108: 3965-3965 [Full Text]
Pasqualucci, L., Liso, A., Martelli, M. P., Bolli, N., Pacini, R., Tabarrini, A., Carini, M., Bigerna, B., Pucciarini, A., Mannucci, R., Nicoletti, I., Tiacci, E., Meloni, G., Specchia, G., Cantore, N., Di Raimondo, F., Pileri, S., Mecucci, C., Mandelli, F., Martelli, M. F., Falini, B. (2006). Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification. Blood 108: 4146-4155 [Abstract] [Full Text]
Garcia, M. A., Gil, J., Ventoso, I., Guerra, S., Domingo, E., Rivas, C., Esteban, M. (2006). Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action. Microbiol. Mol. Biol. Rev. 70: 1032-1060 [Abstract] [Full Text]
Marzac, C., Teyssandier, I., Calendini, O., Perrot, J.-Y., Faussat, A.-M., Tang, R., Casadevall, N., Marie, J.-P., Legrand, O. (2006). Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia. Clin. Cancer Res. 12: 7018-7024 [Abstract] [Full Text]
Heuser, M., Beutel, G., Krauter, J., Dohner, K., von Neuhoff, N., Schlegelberger, B., Ganser, A. (2006). High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 108: 3898-3905 [Abstract] [Full Text]
Falini, B., Martelli, M. P., Bolli, N., Bonasso, R., Ghia, E., Pallotta, M. T., Diverio, D., Nicoletti, I., Pacini, R., Tabarrini, A., Galletti, B. V., Mannucci, R., Roti, G., Rosati, R., Specchia, G., Liso, A., Tiacci, E., Alcalay, M., Luzi, L., Volorio, S., Bernard, L., Guarini, A., Amadori, S., Mandelli, F., Pane, F., Lo-Coco, F., Saglio, G., Pelicci, P.-G., Martelli, M. F., Mecucci, C., for the GIMEMA Acute Leukemia Working Party, (2006). Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia. Blood 108: 1999-2005 [Abstract] [Full Text]
Chen, W., Rassidakis, G. Z., Li, J., Routbort, M., Jones, D., Kantarjian, H., Medeiros, L. J., Bueso-Ramos, C. E. (2006). High frequency of NPM1 gene mutations in acute myeloid leukemia with prominent nuclear invaginations ("cuplike" nuclei).. Blood 108: 1783-1784 [Full Text]
Wilson, C. S., Davidson, G. S., Martin, S. B., Andries, E., Potter, J., Harvey, R., Ar, K., Xu, Y., Kopecky, K. J., Ankerst, D. P., Gundacker, H., Slovak, M. L., Mosquera-Caro, M., Chen, I-M., Stirewalt, D. L., Murphy, M., Schultz, F. A., Kang, H., Wang, X., Radich, J. P., Appelbaum, F. R., Atlas, S. R., Godwin, J., Willman, C. L. (2006). Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction. Blood 108: 685-696 [Abstract] [Full Text]
Cathelin, S., Rebe, C., Haddaoui, L., Simioni, N., Verdier, F., Fontenay, M., Launay, S., Mayeux, P., Solary, E. (2006). Identification of Proteins Cleaved Downstream of Caspase Activation in Monocytes Undergoing Macrophage Differentiation. J. Biol. Chem. 281: 17779-17788 [Abstract] [Full Text]
Li, J., Sejas, D. P., Rani, R., Koretsky, T., Bagby, G. C., Pang, Q. (2006). Nucleophosmin Regulates Cell Cycle Progression and Stress Response in Hematopoietic Stem/Progenitor Cells. J. Biol. Chem. 281: 16536-16545 [Abstract] [Full Text]
Monzo, M., Brunet, S., Urbano-Ispizua, A., Navarro, A., Perea, G., Esteve, J., Artells, R., Granell, M., Berlanga, J., Ribera, J. M., Bueno, J., Llorente, A., Guardia, R., Tormo, M., Torres, P., Nomdedeu, J. F., Montserrat, E., Sierra, J., for CETLAM, (2006). Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia. Blood 107: 4871-4879 [Abstract] [Full Text]
Dohner, K., Dohner, H. (2006). Rush hour in AML: news on NPM traffic. Blood 107: 4200-4201 [Full Text]
Falini, B., Bolli, N., Shan, J., Martelli, M. P., Liso, A., Pucciarini, A., Bigerna, B., Pasqualucci, L., Mannucci, R., Rosati, R., Gorello, P., Diverio, D., Roti, G., Tiacci, E., Cazzaniga, G., Biondi, A., Schnittger, S., Haferlach, T., Hiddemann, W., Martelli, M. F., Gu, W., Mecucci, C., Nicoletti, I. (2006). Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood 107: 4514-4523 [Abstract] [Full Text]
Grimm, T., Holzel, M., Rohrmoser, M., Harasim, T., Malamoussi, A., Gruber-Eber, A., Kremmer, E., Eick, D. (2006). Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex. Nucleic Acids Res 34: 3030-3043 [Abstract] [Full Text]
Thiede, C., Koch, S., Creutzig, E., Steudel, C., Illmer, T., Schaich, M., Ehninger, G., for the Deutsche Studieninitiative Leukamie (DSIL), (2006). Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107: 4011-4020 [Abstract] [Full Text]
Roti, G., Rosati, R., Bonasso, R., Gorello, P., Diverio, D., Martelli, M. F., Falini, B., Mecucci, C., for the Gruppo Italiano Malattie Ematologiche dell, (2006). Denaturing High-Performance Liquid Chromatography: A Valid Approach for Identifying NPM1 Mutations in Acute Myeloid Leukemia. J. Mol. Diagn. 8: 254-259 [Abstract] [Full Text]
Colombo, E., Martinelli, P., Zamponi, R., Shing, D. C., Bonetti, P., Luzi, L., Volorio, S., Bernard, L., Pruneri, G., Alcalay, M., Pelicci, P. G. (2006). Delocalization and Destabilization of the Arf Tumor Suppressor by the Leukemia-Associated NPM Mutant.. Cancer Res. 66: 3044-3050 [Abstract] [Full Text]
Chou, W.-C., Tang, J.-L., Lin, L.-I., Yao, M., Tsay, W., Chen, C.-Y., Wu, S.-J., Huang, C.-F., Chiou, R.-J., Tseng, M.-H., Lin, D.-T., Lin, K.-H., Chen, Y.-C., Tien, H.-F. (2006). Nucleophosmin Mutations in De novo Acute Myeloid Leukemia: The Age-Dependent Incidences and the Stability during Disease Evolution.. Cancer Res. 66: 3310-3316 [Abstract] [Full Text]
Jabbour, E. J., Estey, E., Kantarjian, H. M. (2006). Adult Acute Myeloid Leukemia. Mayo Clin Proc. 81: 247-260 [Abstract] [Full Text]
Pearce, D. J., Taussig, D., Zibara, K., Smith, L.-L., Ridler, C. M., Preudhomme, C., Young, B. D., Rohatiner, A. Z., Lister, T. A., Bonnet, D. (2006). AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML. Blood 107: 1166-1173 [Abstract] [Full Text]

Comments and questions? Please contact us.