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

pts (38.8%) that were isolated (absence of ACA and absence of mutation)
in 6 pts. As duplication could be a consequence of genetic instability, we
then tested the link between BCR-ABL duplications and BCR-ABL TK
mutations. No correlation could be evidenced with the Fisher’s exact test
(p=0.55) and only 5 pts were found to have both BCR-ABL duplication
and mutation, suggesting that the two mechanisms are independent.
Duplications were not associated with primary or secondary resistance
(p=1) whereas mutations are more frequent in the context of secondary
resistance (p=0,01). Conclusions. We have identified an unexpected high
frequency of BCR-ABL duplications (27%) using FISH analysis in samples
from pts resistant to IM. In 2/3 of the cases, these duplications were not
associated with gain of Philadelphia chromosome on conventional cytogenetic.
BCR-ABL duplications were present independently to the detection
of BCR-ABL TKD mutations. Whether this underestimated mechanism
of resistance is correlated with a particular response to second line
TKI remains to be determined.
0959
EXPRESSION OF WT-1, PRAME, RHAMM AND BAALC GENES IN PERIPHERAL BLOOD
OF AML PATIENTS AT DIAGNOSIS
J. Polak, J. Schwarz, J. Marková, J. Maalaufová, Z. Volková,
C. Haskovec
UHKT, PRAGUE 2, Czech Republic
Background. Several genes, including WT-1, PRAME, RHAMM have
been suggested as possible markers of minimal residual disease (MRD)
or prognostic factors in AML patients. Also expression of the BAALC
gene has been proposed as a possible prognostic factor of medical outcome
in AML patients with normal cytogenetics. Aims. The goal of our
study was to test expression of genes mentioned above and to find an
alternative suitable marker of MRD especially for those patients who had
a relatively low expression of the WT-1 gene at presentation. Methods.
The expression of WT-1 and PRAME was measured by the quantitative
real-time PCR with the specific TaqMan probes on the Rotor Gene thermocycler
in peripheral blood of patients and healthy controls; and their
expression was related to expression of the control gene ABL. The
expression of BAALC and RHAMM was quantified using TaqMan?
Gene Expression Assays and was related to the expression of the control
gene ABL-1 - TaqMan ® Gene Expression Assay. The informed consent
was obtained from all patients.
Figure 1. The expression of BAALC in the peripheral blood of AML patients
at diagnosis.
Results. The cDNA level of WT-1 was detected in peripheral leukocytes
from 52 AML patients at diagnosis. The expression of WT-1 was significantly
lower in 8 AML patients with t(8,21), p=0,0004. An elevated
expression of the PRAME and RHAMM genes was found in AML
patients at diagnosis (n=51 and n=70, respectively) compared to their
expression in peripheral blood of normal healthy donors (n=21)
p