Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols
Por:
Ribera, J, Morgades, M, Zamora, L, Montesinos, P, Gomez-Segui, I, Pratcorona, M, Sarra, J, Guardia, R, Nomdedeu, J, Tormo, M, Martinez-Lopez, J, Hernandez-Rivas, JM, Gonzalez-Campos, J, Barba, P, Escoda, L, Genesca, E, Sole, F, Milla, F, Feliu, E, Ribera, JM, Spanish PETHEMA Grp, Spanish Soc Hematology
Publicada:
1 nov 2015
Resumen:
BACKGROUNDSome copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL).
METHODSThis study analyzed via multiplex ligation-dependent probe amplification the frequency and prognostic impact of CNAs of 12 genetic regions in 142 adolescents and adults with de novo precursor B-cell ALL.
RESULTSThe cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion (59 of 142 or 42%) was the most frequent CNA, and it was followed by Ikaros family zinc finger 1 (IKZF1) losses (49 of 142 or 35%). IKZF1 deletions were more prevalent in Philadelphia chromosome (Ph)-positive ALL and were associated with advanced age and high white blood cell (WBC) counts. The multivariate analysis showed that advanced age and early B-cell factor 1 (EBF1) deletions were associated with chemotherapy resistance in both the whole series (hazard ratios, 0.949 and 0.135, respectively) and the Ph-negative subgroup (hazard ratios, 0.946 and 0.118, respectively). High WBC counts and focal IKZF1 deletions correlated with disease recurrence (hazard ratios, 1.005 and 1.869, respectively), whereas advanced age and CDKN2A/B losses influenced overall survival in both the whole series (hazard ratios, 1.038 and 2.545, respectively) and the Ph-negative subgroup (hazard ratios, 1.044 and 2.105, respectively).
CONCLUSIONSDeletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse prognosis for adolescents and adults with B-precursor ALL, and this suggests that these CNAs should be included in the initial risk assessment of ALL. Cancer 2015;121:3809-3817. (c) 2015 American Cancer Society.
Deletions of early B-cell factor 1, cyclin-dependent kinase inhibitor 2A/B, and Ikaros family zinc finger 1 are independent markers of a poor prognosis for uniformly treated adolescent and adult patients with B precursor acute lymphoblastic leukemia.
Filiaciones:
Ribera, J:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Morgades, M:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Zamora, L:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Montesinos, P:
Hosp La Fe, Dept Hematol, E-46009 Valencia, Spain
Gomez-Segui, I:
Hosp La Fe, Dept Hematol, E-46009 Valencia, Spain
Pratcorona, M:
August Pi I Sunyer Inst Biomed Res, Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain
Sarra, J:
Duran I Reynals Hosp, Catalan Inst Oncol, Dept Hematol, Lhospitalet De Llobregat, Spain
Guardia, R:
Josep Trueta Hosp, Catalan Inst Oncol, Dept Hematol, Girona, Spain
Nomdedeu, J:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain
Tormo, M:
Hosp Clin, Dept Hematol, Valencia, Spain
Martinez-Lopez, J:
Doce Octubre Hosp, Dept Hematol, Madrid, Spain
Hernandez-Rivas, JM:
Univ Salamanca, Spanish Natl Res Council, Hosp Clin Univ,Inst Biomed Invest Salamanca, Ctr Invest Canc,Inst Mol & Cellular Biol Canc,Hem, E-37008 Salamanca, Spain
Gonzalez-Campos, J:
Virgen del Rocio Hosp, Dept Hematol, Seville, Spain
Barba, P:
Vall dHebron Hosp, Dept Hematol, Barcelona, Spain
Escoda, L:
Joan XXIII Univ Hosp, Dept Hematol, Tarragona, Spain
Genesca, E:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Sole, F:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Milla, F:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Feliu, E:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
Ribera, JM:
Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Catalan Inst Oncol,Dept Clin Hematol, Badalona 08916, Spain
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