Rescue of genomic information in adult acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics: a GIMEMA centralized biological study |
| |
Authors: | Caterina Matteucci Gianluca Barba Emanuela Varasano Antonella Vitale Marco Mancini Nicoletta Testoni Antonio Cuneo Giovanna Rege‐Cambrin Loredana Elia Roberta La Starza Valentina Pierini Lucia Brandimarte Marco Vignetti Robin Foà Cristina Mecucci |
| |
Institution: | 1. Haematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, University of Perugia, Perugia;2. Department of Cellular Biotechnologies and Haematology, “Sapienza” University of Rome, Rome;3. Institute of Haematology “Lorenzo e Ariosto Seràgnoli”, Sant’Orsola‐Malpighi Hospital, University of Bologna, Bologna;4. Haematology Section, Department of Biomedical Sciences, University of Ferrara, Ferrara;5. Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano, Turin;6. GIMEMA Data Centre, GIMEMA Foundation, Rome, Italy |
| |
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. |
| |
Keywords: | adult acute lymphoblastic leukaemia metaphase/array comparative genomic hybridization NF1/17q11· 2 deletion multiple genomic imbalances bad prognosis |
|
|