Details

Autor(en) / Beteiligte

• MARTINELLI, Giovanni
• IACOBUCCI, Ilaria
• PAPAYANNIDIS, Cristina
• PAOLINI, Stefania
• ELIA, Loredana
• FAZI, Paola
• MELONI, Giovanna
• AMADORI, Sergio
• SAGLIO, Giuseppe
• PANE, Fabrizio
• BACCARANI, Michele
• FOA, Robin
• TIZIAVA STORLAZZI, Clelia
• VIGNETTI, Marco
• PAOLONI, Francesca
• CILLONI, Daniela
• SOVERINI, Simona
• VITALE, Antonella
• CHIARETTI, Sabina
• CIMINO, Giuseppe

Titel

IKZF1 (Ikaros) Deletions in BCR-ABL1–Positive Acute Lymphoblastic Leukemia Are Associated With Short Disease-Free Survival and High Rate of Cumulative Incidence of Relapse: A GIMEMA AL WP Report

Ist Teil von

• Journal of clinical oncology, 2009-11, Vol.27 (31), p.5202-5207

Ort / Verlag

Alexandria, VA: American Society of Clinical Oncology

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The causes of the aggressive nature of BCR-ABL1-positive adult acute lymphoblastic leukemia (ALL) are unknown. To identify, at the submicroscopic level, oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed an investigation of genomic copy number alterations using single nucleotide polymorphism array, genomic polymerase chain reaction, and sequencing of candidate genes. Eighty-three patients with de novo adult Philadelphia chromosome (Ph) -positive ALL were enrolled onto institutional (n = 17) or Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Working Party delle Leucemia Acute (n = 66) clinical trials. Treatments included tyrosine kinase inhibitor (TKI) alone, conventional chemotherapy, or a combination of TKI and chemotherapy. A 7p12 deletion of IKZF1 (Ikaros) was identified in 52 (63%) of 83 patients. The pattern of deletion varied among different patients, but the two most common deletion types were loss of exons 4 to 7 in 31 (37%) of 83 patients and loss of exons 2 to 7 in 17 (20%) of 83 patients. Disease-free survival (DFS) was shorter in patients with IKZF1 deletion versus patients with IKZF1 wild type (10 v 32 months, respectively; P = .02). Furthermore, a significantly shorter cumulative incidence of relapse was recorded in patients with IKZF1 deletion versus patients with IKZF1 wild type (10.1 v 56.1 months, respectively; P = .001). Multivariate analysis confirmed the negative prognostic impact of IKZF1 deletion on DFS (P = .04). We conclude that IKZF1 deletions are likely to be a genomic alteration that significantly affects the prognosis of Ph-positive ALL in adults.