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  • Title: Rescue of genomic information in adult acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics: a GIMEMA centralized biological study.
    Author: Matteucci C, Barba G, Varasano E, Vitale A, Mancini M, Testoni N, Cuneo A, Rege-Cambrin G, Elia L, La Starza R, Pierini V, Brandimarte L, Vignetti M, Foà R, Mecucci C, GIMEMA Acute Leukaemia Working Party, Italy.
    Journal: Br J Haematol; 2010 Apr; 149(1):70-8. PubMed ID: 20067559.
    Abstract:
    Metaphase (M-) and array (A-) Comparative Genomic Hybridization (CGH) were used to investigate 40 cases of T- and 32 of B-cell acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics. M-CGH was performed in all cases and A-CGH in 10/12 T-ALL cases with uncertain/normal M-CGH results. M-CGH was abnormal in 38/72 cases, with a total of 110 imbalances (60 gains, 50 losses). 25/40 patients with T-ALL (62.5%) showed 77 imbalances, with at least 1 genomic imbalance and a mean of 3 aberrations/patient (range 1-12). 13/32 patients with B-ALL (40.6%) presented 34 imbalances, with a mean of 2.6 imbalances (range 1-8). A-CGH detected 4 more T-ALL cases with genomic imbalances. A-CGH identified NF1/17q11.2 deletion and interphase fluorescence in situ hybridization provided a 10.8% estimated overall incidence of NF1/17q11.2 deletion in T-ALL. In all but one case (6/7) with NF1 deletion, denaturing high-performance liquid chromatography and direct sequencing detected NOTCH1 gene mutations. Three or more imbalances in CGH-positive cases were significantly associated with resistance to treatment and death during or after induction therapy. We suggest that the work-up for ALL at diagnosis should include CGH investigations, particularly when cytogenetics is uninformative, because they may provide potentially valuable information with prognostic and therapeutic implications.
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