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

12 th Congress of the European Hematology Association
tively whereas molecular remission defined as a negative RT-PCR for
FIP1L1-PDGFRA fusion gene was recorded after 6 and 24 months respectively.
One patient, who was not initially studied for FIP1L1-PDGFRA
transcript, revelaed CHR after 13 days. In this pt, imatinib was stopped
after 7 months while in CHR and after 5 months off, eosinophilia
recurred. Imatinib at 100 mg daily was resumed and CHR was obtained
in next 2 weeks. Of note, a FIP1L1-PDGFRA fusion gene was not
detectable at relapse. The median follow-up is +24 months (range +24
to+36) and pts receive imatinib at 100mg once weekly with sustained
remission. In 7 pts resulted negative for FIP1L1-PDGFRA fusion gene we
observed 2 transient and short-term haematologic improvement. 2 out
of those 7 pts during follow-up, developed leukemia, one pt was diagnosed
as having chronic eosinophilic leukemia with 10% of blasts in
peripheral blood and he was positive for the JAK2V617F mutation. The
second patient- a 6-year old boy developed acute lymphoblastic
leukemia. Three patients who responded to therapy were younger (54
vs 56yrs), had higher blood eosinophilia count (5.1 vs 3.6), higher bone
marrow eosinophilia infiltration (32 vs 29), lower B12 serum level (288
vs 649 pg/mL), serum IL-5 level (12 vs 23 pg/mL) and serum IgE level (22
vs 89 IU/mL) if compare to 7 pts who failed imatinib. Time to start imatinib
was shorter in responders (50 vs 56 mo). Conclusions. We confirm
high efficacy of imatinib in patients carrying FIP1L1-PDGFRA fusion
gene. In imatinib responders, the dose can be safely reduced to 100 mg
once weekly and it is sufficient to maintain remission.
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THE V617F JAK2 MUTATION INCIDENCE IS HIGHLY REPRESENTED IN BCR/
ABL-NEGATIVE CHRONIC MYELOFERATIVE DISORDERS AND PREDICTABLE BY
SIMPLE HAEMATOLOGICAL PARAMETERS IN PATIENTS WITH ERYTHROCYTOSIS
F. Morabito, 1 E. Lucia, 1 B. Martino, 1 C. Mammi, 2 E. Vigna, 1
C. Mazzone, 1 M. Gentile, 1 M.G. Bisconte, 1 C. Gentile, 1 C. Laganà, 2
F. Nobile, 1 F. Morabito1 1 2 UOC di Ematologia, COSENZA; UOC di Genetica Medica, REGGIO
CALABRIA, Italy
Background. Recently, recurrent and activating G to T point mutation
resulting in substitution of phenylalanine for valine at position 617
(V617F) in the Janus kinase 2 (Jak2) was reported in bcr/abl-negative
chronic myeloproliferative disorders (cMPD), including polycythemia
vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis
(IMF). Estimates, using different detection methods, indicate that
JAK2V617F is present in 65-97% of PV, 23-57% of ET, and 35-57% of
IMF patients, respectively. However, the distribution pattern among
cMPD is changing since more sensitive methods, other than time consuming
and not always feasible sequencing technique, were developed.
Aim. In this study we wonted to establish the V617F JAK2 mutation
incidence in bcr/abl-negative cMPD and to predict JK2 mutational status,
by using simple haematological parameters, in those cases presenting
with erythrocytosis. Methods.We used an allele-specific polymerase
chain reaction (PCR) assay (designated as the AS-PCR assay) to detect
JAK2V617F. Briefly, a mutation-specific forward primer containing a fluorescent
tag (FAM) was used in a PCR reaction with a wild-type
sequence reverse primer. Only mutated DNA will be amplified (203bp),
if present, and the PCR reaction product was analyzed using capillary
electrophoresis in an automated genetic analyzer. To evaluate the sensitivity
of the technique employed, either bone marrow (BM) or peripheral
blood (PB) were analyzed, while the background signal was examined
by using 50 normal PB samples. Results. All normal samples resulted
negative, showing a median signal one log lower than cases belonging
to positive PB samples obtained from cMPD. JAK2V617F mutated
cMPD BM samples showed a fairly expected two logs higher signal than
normal controls. We analyzed 38 PV, 43 TE, 24 MIF, 20 bcr/abl cMPD
and 22 secondary polyglobulia (secPoly). Out of 147 cases analysed, 100
resulted JAK2 mutated. In particular, none of secPoly cases resulted
mutated, while 94.7%, 76.7%, 70.8% and 70.0% showed JAK2V617F
mutation in PV, TE, MIF and cMPD, respectively. Next, we pooled PV
and secPoly trying to predict JK2 mutational status by using 3 simple
parameters, i.e. Ht level, and WBC and PLT count. By using ROC curve
analysis, we determined 320×10 9 /L (AUC=0.925, p