2008 Barcelona - European Society of Human Genetics

Cancer genetics
genes . One of them had two additional unbalanced translocations,
t(12;14)(p;q11) and t(12;16)(p;p) with complex karyotype such as
45,XY,-14,t(11;17)(q23;q21),der(12)t(12;14)(p11;q11),der(16)t(?12;1
6)(p11;q13) in 96% cells . It has been reported that such variant cases
are resistant to ATRA and exhibit no therapeutic response, though
resemble PML-RARA morphologically. Therefore, these two patients
are presumed to experience poor prognosis . Investigation of all these
cases by FISH for PML-RARA would have given normal result to these
two patients and could have led to progression of the disease condition
. Therefore, it´s understood that conventional cytogenetics still
plays an important role in diagnosis, classification, prognostication and
monitoring of hematologic malignancies in the era of microarray technology
and cannot be replaced by any other molecular technique .
P04.077
cytogenetic study of chronic myeloid leukemia (cmL)
R. Joshi, B. B. Ganguly;
MGM Centre for Genetic Research & Diagnosis, New Bombay, India.
To explore the clinical cytogenetic feature & prognosis of chronic
myeloid leukemia patient, evaluation of 8 CML cases (6 men and 2
women) from the indian population with ages ranging from 25 to 55
years were studied in the present dissertation project . Bone marrow
samples were processed following direct method &/or 24hrs culture
without mitogen for chromosome preparation and karyotype analysis
of G-banded metaphases . 25 metaphases were studied for each
case using karyotyping software (Metasystems, Germany) . All 8 cases
showed Philadelphia chromosome i .e . t(9;22)(q34;q11) in 100% cells .
Two (25%) cases showed extra Philadelphia chromosome in 8% &
38% cells respectively . One case had missing of Y chromosome in
addition to Philadelphia chromosome . It has been established that the
major secondary chromosomal abberation in adult is double philadelphia
chromosome & minor one is -Y chromosome . The i(17)q is not
very common in adult . Since chromosome 17 was normal in all the
above cases the prognosis of these patients will be comparetively better
. However, the prognosis of patient in which abnormal metaphase
with +ph chromosome was 38% expected to be poor compared to the
patient with 8 .6% abnormal metaphases . Due to the additional chromosomal
abnormality, patient may aquire resistance to Imatinib - the
tyrosine kinase inhibitor . Therefore, it is understood that cytogenetic
study is important in diagnosis & prognostication of CML patient .
P04.078
Another case with der(8)t(8;17)(p11;q11) in sézary’s syndrome
A. Valera1,1 , A. Carrió1 , D. Costa1 , A. Arias1 , M. Rozman1 , M. Aymerich1 , D.
Colomer1 , P. Abrisqueta2 , F. Bosch2 , T. Estrach3 , E. Campo1 ;
1Unitat d’Hematopatologia. Hospital Clínic de Barcelona., Barcelona, Spain,
2 3 Servei d’Hematologia.Hospital Clínic de Barcelona, Barcelona, Spain, Servei
de Dermatologia.Hospital Clínic de Barcelona, Barcelona, Spain.
Sézary’s syndrome (SS) is a peripheral T-cell neoplasm characterized
by a pruritic exfoliative or infiltrated erythroderma, lymphadenopaties,
and atypical T lymphocytes in the periphereal blood . Chromosome
abnormalities, mostly complex karyotypes, are seen in about 50% of
patients with SS, and there have only been a few instances of recurrent
rearrangements .
We report a 60 year-old female referred to Hematology Service due to
20 months history of lymphocytosis . The patient showed a cutaneous
hyperpigmentation and bilateral axillary and inguinal lymphadenopaties
. The peripheral blood smear presented 40% of Sézary cells . The
diagnosis was Mycosis Fungoide with leukemic involvement .
The karyotype in peripheral blood was performed . We used G-banded
technique in conventional cytogenetics . Molecular cytogenetics
(FISH analysis) permitted discovering the rearrangements involved .
The whole chromosome paints (WCPs) for chromosomes 1, 5, 9, 10,
11, 15, 17 and 19 were used . Finally the karyotype was: 44-45, XX,
t(1;5)(p33;q31)[4], der(8)t(8;17)(p11;q11)[4], -9[2], inv(9)(p21;q34)[2],
-10[4], del(11)(q21)[4], der(14)t(10;14)(?q?;p11)[4], del(15)(q22)[4],
der(15)t(9;15)(q21;q26)[2], -17[4], +mar1[4] [cp4] / 45, X, -X[6] /
46,XX[10] .
Cytogenetic alterations were concordant with other abnormalities described
before in SS, like: breakpoints at 1p32-36 and 10q23-26, and
other alterations involving chromosomes 8, 9, 11 and 17 . But the most
important event was the presence of der(8)t(8;17)(p11;q11), because
to our knowledge, this is the fourth case with the same alteration re-
ported in SS . First of all was Thangavelu M, et al . Blood (1997) with
two cases with der(8)t(8;17)(p11;q11) and a psu dic(17;8)(p11 .2;p11 .2)
was observed by Batista D, et al . Genes, Chromosomes and Cancer
(2006) .
P04.079
Der(1;16)(q10;p10) in Acute Myeloid Leukemia: the first female
case described
N. Kokalj Vokac1 , A. Zagorac1 , A. Erjavec Skerget1 , Z. Roskar1 , H. Podgornik2 ,
P. Cernelc2 ;
1 2 University Medical Centre Maribor, 2000 Maribor, Slovenia, University Medical
Centre Ljubljana, 1000 Ljubljana, Slovenia.
Whole-arm translocation of chromosome 1 and 16 is recurrently observed
in non-hematologic neoplasias such as breast carcinomas and
Ewings sarcoma but rarely in hematologic neoplasias, mostly in multiple
myelomas . To our knowledge, only 7 cases were described in
MDS/AML, interesting all were males .
Here we describe the first female patient with AML M4/M5 with
der(1;16)(q10;p10) as the sole chromosome rearrangement found .
Cytogenetic examination of bone marrow cells revealed that the normal
chromosome 16 was lost and replaced by an abnormal chromosome
consisting of the long arm of chromosome 1 and the short arm of
chromosome 16, resulting in trisomy of the long arm of chromosome
1 and monosomy of the long arm of chromosome 16 . The karyotype
was confirmed by FISH: 46,XX,+1,der.ish (1;16)(q10;p10)(wcp1+,wcp
16+,cep16+) .
Due to a small number of metaphases available and bad resolution of
chromosomes, CGH was also performed. Only the amplification of the
long arm of chromosome 1 and deletion of the long arm of chromosome
16 was confirmed.
Unfavorable outcome, including no response to chemotherapy, and
short survival were characteristic of our patient . Despite very short survival
of our patient, prognostic significance remains to be determined.
It is possible that some other unidentified molecular mechanism could
play a role in bad prognosis or simply the fact that this is the only
female patient described until now . From this point of view, the pathogenesis
of der(1;16) still remains unresolved .
P04.080
Detection of gene expression profile for BAALC and WT1 genes
by real time Rt-PcR in patients with acute myeloid leukemia
L. A. Tamas, E. Seclaman, A. Mihala, A. Neghina, C. Samoila, I. M. Ciuca;
University of Medicine and Pharmacy, Timisoara, Romania.
Acute myeloid leukemia (AML) is a heterogeneous group of diseases
characterized by uncontrolled proliferation of clonal neoplastic hematopoietic
precursor cells and impaired production of normal hematopoiesis
leading to neutropenia, anemia, and thrombocytopenia .
High mRNA expression of BAALC and WT1 have been shown to be
an adverse risk factor in newly diagnosed AML patients with normal
cytogenetics .
Independent confirmation is required to validate the initial results so
that BAALC and WT1 expression may be exploited for risk-adapted
treatment stratification of AML patients with normal cytogenetics.
We analyzed patients selected from newly diagnosed cases of AML
and a control group of healthy individuals .
Total RNA from leukocytes was extracted from blood samples treated
with RNA-later (QIAGEN) following the manufacturer’s directions
(RiboPure - blood kit, Ambion) . For semiquatitative RT-PCR we used
One-step RT-PCR kit (QIAGEN), with gene-specific, intron spanning
primers for BAALC,WT1 and GPDH as housekeeping gene. Comparative
real-time RT-PCR assays were performed for each sample in triplicate
.
The results showed a significantly increased level of expression for
BAALC and WT1genes in de novo acute myeloid leukemia patients
with normal cytogenetics comparative with healthy individuals from the
control group .
In conclusion, the analyse of BAALC and WT1 genes expression in
AML patients is a molecular marker which can be used for the evaluation
of disease aggressivenes and prognosis for patients with normal
cytogenetics .
Acknowledgements: The study was supported by a romanian research
grant CEEX 5855/2006
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