Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols

Jordi Ribera, Mireia Morgades, Lurdes Zamora, Pau Montesinos, Inés Gõmez-Seguí, Marta Pratcorona, Josep Sarrà, Ramon Guàrdia, Josep Nomdedeu, Mar Tormo, Joaquin Martínez-Lopez, Jesús María Hernández-Rivas, José González-Campos, Pere Barba, Lourdes Escoda, Eulàlia Genescà, Francesc Solé, Fuensanta Millá, Evarist Feliu, Josep Maria Ribera

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32 Citations (Scopus)

Abstract

© 2015 American Cancer Society. BACKGROUND Some copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL). METHODS This 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. RESULTS The 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). CONCLUSIONS Deletions 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.
Original languageEnglish
Pages (from-to)3809-3817
JournalCancer
Volume121
Issue number21
DOIs
Publication statusPublished - 1 Nov 2015

Keywords

  • acute lymphoblastic leukemia
  • adult
  • B precursor
  • copy number alterations
  • prognosis

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