A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia

George Adrian Calin, Manuela Ferracin, Amelia Cimmino, Gianpiero Di Leva, Masayoshi Shimizu, Sylwia E. Wojcik, Marilena V. Iorio, Rosa Visone, Nurettin Ilfer Sever, Muller Fabbri, Rodolfo Iuliano, Tiziana Palumbo, Flavia Pichiorri, Claudia Roldo, Ramiro Garzon, Cinzia Sevignani, Laura Rassenti, Hansjuerg Alder, Stefano Volinia, Chang Gong LiuThomas J. Kipps, Massimo Negrini, Carlo M. Croce

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgVH) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities. RESULTS: A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgVH from those with mutated IgVH. The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P

Original languageEnglish
Pages (from-to)1793-1801
Number of pages9
JournalNew England Journal of Medicine
Volume353
Issue number17
DOIs
Publication statusPublished - Oct 27 2005

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B-Cell Chronic Lymphocytic Leukemia
MicroRNAs
ZAP-70 Protein-Tyrosine Kinase
B-Lymphocytes
Genes
Immunoglobulin Heavy Chains
Mutation
Germ-Line Mutation
Germ Cells
Disease Progression
Alleles

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E., ... Croce, C. M. (2005). A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New England Journal of Medicine, 353(17), 1793-1801. https://doi.org/10.1056/NEJMoa050995

A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. / Calin, George Adrian; Ferracin, Manuela; Cimmino, Amelia; Di Leva, Gianpiero; Shimizu, Masayoshi; Wojcik, Sylwia E.; Iorio, Marilena V.; Visone, Rosa; Sever, Nurettin Ilfer; Fabbri, Muller; Iuliano, Rodolfo; Palumbo, Tiziana; Pichiorri, Flavia; Roldo, Claudia; Garzon, Ramiro; Sevignani, Cinzia; Rassenti, Laura; Alder, Hansjuerg; Volinia, Stefano; Liu, Chang Gong; Kipps, Thomas J.; Negrini, Massimo; Croce, Carlo M.

In: New England Journal of Medicine, Vol. 353, No. 17, 27.10.2005, p. 1793-1801.

Research output: Contribution to journalArticle

Calin, GA, Ferracin, M, Cimmino, A, Di Leva, G, Shimizu, M, Wojcik, SE, Iorio, MV, Visone, R, Sever, NI, Fabbri, M, Iuliano, R, Palumbo, T, Pichiorri, F, Roldo, C, Garzon, R, Sevignani, C, Rassenti, L, Alder, H, Volinia, S, Liu, CG, Kipps, TJ, Negrini, M & Croce, CM 2005, 'A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia', New England Journal of Medicine, vol. 353, no. 17, pp. 1793-1801. https://doi.org/10.1056/NEJMoa050995
Calin, George Adrian ; Ferracin, Manuela ; Cimmino, Amelia ; Di Leva, Gianpiero ; Shimizu, Masayoshi ; Wojcik, Sylwia E. ; Iorio, Marilena V. ; Visone, Rosa ; Sever, Nurettin Ilfer ; Fabbri, Muller ; Iuliano, Rodolfo ; Palumbo, Tiziana ; Pichiorri, Flavia ; Roldo, Claudia ; Garzon, Ramiro ; Sevignani, Cinzia ; Rassenti, Laura ; Alder, Hansjuerg ; Volinia, Stefano ; Liu, Chang Gong ; Kipps, Thomas J. ; Negrini, Massimo ; Croce, Carlo M. / A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. In: New England Journal of Medicine. 2005 ; Vol. 353, No. 17. pp. 1793-1801.
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T1 - A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia

AU - Calin, George Adrian

AU - Ferracin, Manuela

AU - Cimmino, Amelia

AU - Di Leva, Gianpiero

AU - Shimizu, Masayoshi

AU - Wojcik, Sylwia E.

AU - Iorio, Marilena V.

AU - Visone, Rosa

AU - Sever, Nurettin Ilfer

AU - Fabbri, Muller

AU - Iuliano, Rodolfo

AU - Palumbo, Tiziana

AU - Pichiorri, Flavia

AU - Roldo, Claudia

AU - Garzon, Ramiro

AU - Sevignani, Cinzia

AU - Rassenti, Laura

AU - Alder, Hansjuerg

AU - Volinia, Stefano

AU - Liu, Chang Gong

AU - Kipps, Thomas J.

AU - Negrini, Massimo

AU - Croce, Carlo M.

PY - 2005/10/27

Y1 - 2005/10/27

N2 - BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgVH) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities. RESULTS: A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgVH from those with mutated IgVH. The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P

AB - BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgVH) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities. RESULTS: A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgVH from those with mutated IgVH. The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P

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