Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia
Por:
Rossi, D, Rasi, S, Spina, V, Bruscaggin, A, Monti, S, Ciardullo, C, Deambrogi, C, Khiabanian, H, Serra, R, Bertoni, F, Forconi, F, Laurenti, L, Marasca, R, Dal-Bo, M, Rossi, FM, Bulian, P, Nomdedeu, J, Del Poeta, G, Gattei, V, Pasqualucci, L, Rabadan, R, Foa, R, Dalla-Favera, R, Gaidano, G
Publicada:
21 feb 2013
Resumen:
The identification of new genetic lesions in chronic lymphocytic leukemia (CLL) prompts a comprehensive and dynamic prognostic algorithm including gene mutations and chromosomal abnormalities and their changes during clonal evolution. By integrating mutational and cytogenetic analysis in 1274 CLL samples and using both a training-validation and a time-dependent design, 4 CLL subgroups were hierarchically classified: (1) high-risk, harboring TP53 and/or BIRC3 abnormalities (10-year survival: 29%); (2) intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 (10-year survival: 37%); (3) low-risk, harboring +12 or a normal genetics (10-year survival: 57%); and (4) very low-risk, harboring del13q14 only, whose 10-year survival (69.3%) did not significantly differ from a matched general population. This integrated mutational and cytogenetic model independently predicted survival, improved CLL prognostication accuracy compared with FISH karyotype (P < .0001), and was externally validated in an independent CLL cohort. Clonal evolution from lower to higher risk implicated the emergence of NOTCH1, SF3B1, and BIRC3 abnormalities in addition to TP53 and 11q22-q23 lesions. By taking into account clonal evolution through time-dependent analysis, the genetic model maintained its prognostic relevance at any time from diagnosis. These findings may have relevant implications for the design of clinical trials aimed at assessing the use of mutational profiling to inform therapeutic decisions.
Filiaciones:
Rossi, D:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Rasi, S:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Spina, V:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Bruscaggin, A:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Monti, S:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Ciardullo, C:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Deambrogi, C:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Khiabanian, H:
Columbia Univ, Dept Biomed Informat, New York, NY USA
Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA
Serra, R:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Lab Med Informat, I-28100 Novara, Italy
Bertoni, F:
IOR Inst Oncol Res, Lymphoma & Genom Res Program, Bellinzona, Switzerland
Oncol Inst Southern Switzerland, Lymphoma Unit, Bellinzona, Switzerland
Forconi, F:
Univ Southampton, CRUK Clin Ctr, Canc Sci Unit, Southampton, Hants, England
Univ Siena, Div Hematol, I-53100 Siena, Italy
Laurenti, L:
Univ Cattolica Sacro Cuore, Inst Hematol, I-00168 Rome, Italy
Marasca, R:
Univ Modena & Reggio Emilia, Dept Hematol & Oncol, Div Hematol, Modena, Italy
Dal-Bo, M:
Ctr Riferimento Oncol, I-33081 Aviano, Italy
Rossi, FM:
Ctr Riferimento Oncol, I-33081 Aviano, Italy
Bulian, P:
Ctr Riferimento Oncol, I-33081 Aviano, Italy
Nomdedeu, J:
Hosp Santa Creu & Sant Pau, Dept Hematol & Lab, Barcelona, Spain
Del Poeta, G:
Univ Roma Tor Vergata, Dept Hematol, Rome, Italy
Gattei, V:
Ctr Riferimento Oncol, I-33081 Aviano, Italy
Pasqualucci, L:
Columbia Univ, Inst Canc Genet, New York, NY USA
Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA
Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA
Univ Perugia, Dept Hematol & Clin Immunol, Inst Hematol, I-06100 Perugia, Italy
Rabadan, R:
Columbia Univ, Dept Biomed Informat, New York, NY USA
Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA
Foa, R:
Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Div Hematol, I-00185 Rome, Italy
Dalla-Favera, R:
Columbia Univ, Inst Canc Genet, New York, NY USA
Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA
Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA
Columbia Univ, Dept Genet & Dev, New York, NY USA
Gaidano, G:
Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, I-28100 Novara, Italy
Green Published, Bronze
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