12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
rearrangements. This large series of cases provides evidence for the
applicability and robustness of iFISH on paraffin embedded tissue in a
routine diagnostic setting, where the presence of a specific abnormality
is essential in confirming the diagnosis. A high proportion of patients
have abnormal patterns and the failure rate is very low. iFISH performed
on thin paraffin sections is rapid, very reliable and relatively inexpensive
and can be integrated into diagnostic laboratories and allows for definitive
diagnostic testing and risk stratification in real time.
0138
NPM1 HAPLOINSUFFICIENCY IN MDS/AML WITH DEL(5Q)/MONOSOMY 5
R. La Starza, 1 G. Roti, 1 L. Brandimarte, 1 E. Varasano, 1 F. Arcioni, 1
A. Pierini, 1 B. Crescenzi, 1 D. Diverio, 2 G. Guglielmini, 3 M.F. Martelli, 1
A. Aventin, 4 C. Mecucci1 1 Hematology, University of Perugia, PERUGIA, Italy; 2 Hematology, University
La Sapienza, ROME, Italy; 3 Internal and Vascular Medicine, PERUGIA, Italy;
4 Hematologia, H De La Santa Creu, BARCELONA, Spain
Background. NPM1, a gene mapping at band 5q35, is implicated in different
forms of leukaemia and NPM1 haploinsufficiency induces
preleukemic MDS-like features in mice. It is not known whether NPM1
is involved in the pathogenesis of MDS/AML with del(5)(q)/-5 which
occurs as an isolated change or as part of complex karyotypes in MDS
and in AML. Aims. To study NPM1 genomic status in MDS/AML with
del(5)(q)/-5 by fluorescence in situ hybridization (FISH) and denaturing
high-performance liquid chromatography (DHPLC). Methods. We studied
58 patients with MDS and 47 with AML (total 105 patients), all bearing
del(5q)/-5 which was isolated or associated with 1 other aberration
in 51 cases and included in complex karyotypes in 54. FISH was done
with the following DNA clones for the long arm of chromosome 5: centromere-
LSI EGR1/D5S721/D5S23 5q31-LSI CSF1R/ D5S721/D5S23
5q34 (Vysis, Abbott, Italy) - RP11-117L6 (NPM1/5q35.1) - CTC-286C20
(FGFR4/5q35.2) - CTC-549A4 (NSD1/5q35.3) - RP1-240G13 (5qter) -
telomere. Cut-off limits for monosomy/deletion in interphase analyses
were the highest values in normal samples (4% for RP11-117L6, 7% for
CTC-286C20, 6.5% for CTC-549A4, 8% for RP1-240G13). Exon 12
NPM1 mutations were studied by DHPLC in 57/105 patients (20 with
isolated del(5q)/-5; 37 with complex karyotypes). Results. FISH detected
NPM1 deletion in 10/58 (17%)patients with MDS and in 22/47 (47%)
with AML (Fisher’s exact test, p