Giuseppe Saglio

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

PURPOSEnThe 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.nnnPATIENTS AND METHODSnEighty-three patients with de novo adult Philadelphia chromosome (Ph) -positive ALL were enrolled onto institutional (n = 17) or Gruppo Italiano Malattie Ematologiche Maligne dellAdulto 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.nnnRESULTSnA 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).nnnCONCLUSIONnWe conclude that IKZF1 deletions are likely to be a genomic alteration that significantly affects the prognosis of Ph-positive ALL in adults.

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-α-based therapy

We measured using a competitive quantitative polymerase chain reaction-capillary electrophoresis (PCR-CE)-based assay, the levels of bcr-abl transcripts in 44 patients with chronic myeloid leukemia (CML) after interferon-α (IFN-α) therapy, who achieved a major (10 patients, MCR group) or complete (34 patients, CCR group) cytogenetic response. All 34 CCR patients had molecular evidence of residual disease detected in bone marrow samples at the time of best karyotypic response. The median number of bcr-abl transcripts of 34 evaluable patients in the CCR group at the time of complete cytogenetic remission was 4/μg RNA (range 3–4600), while the median number of bcr-abl transcripts of 10 patients in the MCR group at the time of best cytogenetic response was 4490/μg RNA (range 600–23u2009900) (Pu2009=u20090.000024). In nine CCR and five MCR patients we were able to quantify the amount of bcr-abl transcript both at diagnosis and after interferon therapy: no statistical difference (Pu2009=u20090.18) was found between the two groups at diagnosis (median bcr-abl transcripts/μg RNA was 30u2009000 vs 39u2009650, respectively). During IFN-α therapy, the two groups were evaluable at the time of major karyotypic conversion: at this point, there was a statistical difference of expression of bcr-abl transcript between the CCR group (17 patients) (median 2700; range 76–40u2009000) and the MCR group (10 patients) (median 4490; range 600–23u2009900), respectively (Pu2009=u20090.046). No differences of bcr-abl amount of transcript were found in patients with CCR obtained either by IFN-α therapy alone (20 patients) vs IFN-α plus ABMT (13 patients) (Pu2009=u20090.47). We firstly demonstrated that although the CCR and MCR groups were clinically, cytogenetically and molecularly indistinguishable at diagnosis, the two groups could be recognized successfully during interferon therapy based on the level of bcr-abl transcript. Bone Marrow Transplantation (2000) 25, 729–736.

Concomitant expression of the rare E1/A3 and B2/A3 types of BCR/ABL transcript in a chronic myeloid leukemia (CML) patient.

Concamitant expression of the rare E1/A3 and B2/A3 types of BCR/ABL transcript in a chronic myeloid leukemia (CML) patient

Translisin recognition site sequences flank translocation breakpoints in a Philadelphia chromosome positive chronic myeloid leukemia patient expressing a novel type of chimeric BCR-ABL transcript (E8-INT-A2)

Translisin recognition site sequences flank translocation breakpoints in a Philadelphia chromosome positive chronic myeloid leukemia patient expressing a novel type of chimeric BCR-ABL transcript (E8-INT-A2)

Response to imatinib mesylate in patients with the FIP1L1-PDGFR-alpha positive hypereosinophilic syndrome: Update of a multicenter prospective study and guidelines for eosinophilia diagnosis

7034 Background: The hypereosinophilic syndrome (HES) may be associated with the fusion of the PDGFRα gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated tyrosine kinase...