2008 Barcelona - European Society of Human Genetics

Cancer genetics
P04.072
Acute promyelocytic leukemia relapsing as secondary acute
myelogenous leukemia with t(3;21)(q26;q22): molecular
characterization and clinical follow-up in a patient with AME
fusion transcript and review of the literature
T. Park 1 , J. Song 1 , K. Lee 1 , Y. Min 2 , S. Lee 1 , Y. Park 1 , J. Kim 1 , O. Kwon 3 , R.
Park 4 , S. Hwang 5 , E. Lee 5 , J. Choi 1 ;
1 Department of Laboratory Medicine, Yonsei University College of Medicine,
Seoul, Republic of Korea, 2 Department of Internal Medicine, Yonsei University
College of Medicine, Seoul, Republic of Korea, 3 Department of Laboratory
Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea,
4 Department of Laboratory Medicine, Soonchunhyang University Hospital,
Seoul, Republic of Korea, 5 Department of Laboratory Medicine, Pusan National
University School of Medicine, Busan, Republic of Korea.
Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous
leukemia (AML) that is characterized by peculiar clinical and
biologic features such as severe hemorrhagic diathesis, specific chromosomal
aberration with t(15;17)(q22;q12), and distinct morphologic
features with predominant abnormal promyelocytes . In contrast to other
subtypes of AML, APL has a particular sensitivity to treatment with
all trans-retinoic acid (ATRA) combined with chemotherapy; converting
this once frequently fatal leukemia to a highly curable disease . However,
therapy-related myelodysplastic syndrome/acute myelogenous
leukemia (t-MDS/AML) has been rarely reported as a late complication
of chemotherapy in APL . To our knowledge, 30 APL cases have
been described as t-MDS/AML in the literature . Among these reports,
only one case relapsed as an acute leukemia with t(3;21)(q26;q22) .
Here we describe a 48-year-old female who was diagnosed with APL
relapsing as a secondary AML with t(3;21) . In this study, chromosome
analysis as well as fluorescent in situ hybridization (FISH), multi-color
FISH (mFISH), and reverse transcriptase-polymerase chain reaction
(RT-PCR) for AML1/MDS1/EVI1 (AME) fusion transcript were performed
. Although allogenic peripheral blood stem cell transplantation
(PBSCT) was done, bone marrow biopsy after PBSCT still revealed
leukemic marrow in this patient .
P04.073
Array-cGH analysis of turkish adult ALL patients
S. Berker-Karauzum 1 , D. Yasar 1 , I. Karadogan 1 , G. Alanoglu 2 , G. Luleci 1 , J. J.
Dermody 3 , G. A. Toruner 3 ;
1 Akdeniz University, Faculty of Medicine, Antalya, Turkey, 2 Suleyman Demirel
University, Faculty of Medicine, Isparta, Turkey, 3 UMDNJ-NJ Medical School,
Newark, NJ, United States.
In basic cytogenetic analysis 40-50% of acute lymphoblastic leukemia
(ALL) patients show a normal karyotype . ALL is a clinically heterogeneous
group, but cryptic copy number alterations could explain some
of the heterogeneity . Array based comparative genomic hybridization
(array-CGH) allows genome-wide high-resolution analysis of copy
number alterations that are not detectable by standard methods including
fluorescence in situ hybridization (FISH) or comparative genomic
hybridization (CGH) . There are reports of array-CGH studies on leukemia
patients, but to our knowledge no published array-CGH studies
exist on adult ALL . In order to asses the diagnostic yield of array-CGH
on adult ALL, we performed pilot experiments on 14 adult ALL cases
using catalog Agilent 44K oligonucleotide arrays . Eleven (78%) ALL
patients had cryptic chromosomal aberrations . Deletions including the
loci at 9p22.2 (n=2), 11p14.1 (n=2), 7p22.3 (n=2), and amplifications
including the loci at 16p13 .12 (n=2), 19q13 .32 (n=2) are observed in
at least two different patients . Our preliminary results indicate that array
CGH analysis provide additional information about cryptic genetic
aberrations during cytogenetic studies of adult ALL patients .
P04.074
Der(7;10)(p10;q10) in acute myeloid leukemia
H. Podgornik, A. Prijatelj, P. Cernelc;
Department of Hematology, Ljubljana, Slovenia.
We report a case of a female patient with der(7;10)(q10;q10) resulting
in loss of long arm of chromosome 7 that has an established prognostic
value in haematological malignancies . In acute myeloblastic leukemia
(AML) most often deletion (7q) and monosomy 7 are observed . Both
changes are classified as poor prognostic criteria. Whole-arm translocations
of chromosome 7 are rarely described . Translocation with the
long arm of chromosome 1 occurs nonrandomly in myelodysplastic
syndrome and AML. While there have been reports on significantly
better clinical outcome than other -7/7q cases the same rearrangement
was also recognized as very poor prognostic feature .
In april 2007 a 23-year old woman was admitted to the hospital . Diagnosis
workup confirmed myelo-monocitic leukemia (AML M4/M5).
Cytogenetic examination of bone marrow cells revealed that one normal
chromosome 7 and 10 were lost and replaced by an abnormal
chromosome consisting of the long arm of chromosome 10 and the
short arm of chromosome 7 . Additionally, a small marker chromosome
was observed in all analyzed metaphases . The whole-arm exchange
was confirmed by FISH using WCP and CEP probes as well as a locus
specific probe (7q32). Combining the results of standard and molecular
cytogenetics the karyotype was interpreted as: 46,XX,der(7;10)(p
10;q10),+mar . The marker chromosome was found to consist of the
chromosome 7 centromeric material . The patient is in cytogenetic remission
now. Her condition will be further followed to clarify the significance
of this chromosomal change . According to our best knowledge it
was not described in hematological malignancies before .
P04.075
Gains of chromosome 2p in chronic lymphocytic leukemia
M. Holzerova 1 , H. Urbankova 1 , R. Plachy 1 , L. Kucerova 2 , Z. Pikalova 1 , T. Papajik
1 , K. Indrak 1 , M. Jarosova 1 ;
1 Department of Hemato-Oncology, University Hospital and Palacky University,
Olomouc, Czech Republic, 2 Department of Pathology, University Hospital and
Palacky University, Olomouc, Czech Republic.
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia
. The progress in molecular genetic characterization of CLL
confirmed the prognostic role of IgV H mutational status, expression of
CD38, as well as chromosomal abnormalities defined by molecular
cytogenetic methods . However, besides chromosomal changes with
known prognostic impact, such as deletions of 6q, 11q (ATM), 13q,
17p (p53) detected routinely, the other additional abnormalities can
be found . It is presently not clear whether other aberrations that are
not detected by the standard FISH panel have any impact on prognosis
and disease progression . Therefore, we performed clinical and
laboratory analysis of 7 CLL patients (males) with detected gains of
chromosome 2p . The aim of the genetic study was supported by the
fact, that gains of genetic material can lead to oncogenic activation of
protooncogenes located within the gained regions . Since 2p23~p11
harbors many protooncogenes already known to be involved in human
tumorigenesis, we desided to check a few selected genes: ALK, N-
MYC, REL, BCL11a and their protein levels .
Comparative genomic hybridization (CGH) or 1 Mb arrayCGH revealed
gain of 2p23~p11 region . For detailed mapping of gained region
we used iFISH with commercial available and BAC-derived probes . In
all cases IgV H mutational pattern was established and immunohistochemical
analysis of selected proteins was performed .
Our study will summarize molecular cytogenetic, molecular genetic
and clinical findings with respect to the 2p abnormalities in 7 CLL patients
.
This work is supported by grant MSM 6198959205 and NR 9484-3.
P04.076
cytogenetic study of variant acute promyelocytic leukemia
B. B. Ganguly;
MGM Centre for Genetic Research & Diagnosis, MGM’s New Bombay Hospital,
New Bombay, India.
Hematologic malignancies are heterogeneous group of clonal hematopoietic
stem cell disorders resulting from wide spectrum of nonrandom
chromosome abnormalities ranging from balanced translocations
to unbalanced karyotypes with numerical and/or structural gains or
losses and to complex rearrangements involving three or more chromosome
abnormalities . In >95% acute promyelocytic leukemia (APL),
t(15;17) is the hallmark of pathogenesis while remaining cases have
cryptic insertion or more complex rearrangements where RARA is constantly
involved . The fusion of PML-RARA disrupts the normal interaction
of retinoic acid and RARA, and converts RARA into a transcription
activator . All-trans retinoic acid receptor (ATRA) is able to interact with
this mechanism and prevent life-threatening thromboembolic/bleeding
complications . We have investigated 30 APL patients by conventional
G-banding and detected two (7%) cases with t(11;17)(q23;q22), which
leads to fusion of PLZF (promyelocytic leukemia zinc finger) and RARA
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